imtoken官方网址|myc基因

作者： imtoken官方网址

2024-03-17 11:27:47

肿瘤研究领域热门基因之MYC - 知乎

肿瘤研究领域热门基因之MYC - 知乎切换模式写文章登录/注册肿瘤研究领域热门基因之MYC赛业生物cyagen咨询业务+v：cyagen-class（备注知乎）想调整研究方向，获得学术研究突破口？想获得国自然选题思路，提高国自然基金申报成功率？你需要了解学科发展态势和未来走向！赛业生物专栏《Gene of the Week》每周会根据热点研究领域介绍一个基因，详细为您介绍基因基本信息、研究概况和应用背景等，助您保持学术研究敏锐度，提高科学研究效率，期待您的持续关注哦。今天我们要讲的主角是明星致癌基因MYC。MYC基因研究概况近年来的研究发现，肿瘤产生的根本原因是基因的变异。基因是遗传信息的基本单位，总的来说，细胞中有两类基因与肿瘤的发生发展密不可分，它们分别是原癌基因与抑癌基因。MYC基因是目前研究最多的一类核蛋白类癌基因，包括C—MYC、N—MYC、L—MYC、R—MYC 4种。C-MYC原癌基因是最常见的活化原癌基因之一，C-MYC参与调控的癌症占人类所患癌症的20%左右，受C-MYC原癌基因影响致死的癌症患者每年可达几十万。MYC是一种作用广泛的转录因子，它通过多种机制调节细胞的分化和增殖，包括靶基因的转录扩增。图1.MYC调控细胞生长和增殖。DOI:10.1016/j.cell.2012.03.003。C-MYC基因主要通过扩增和染色体易位重排的方式激活，与某些组织肿瘤的发生、发展和演变转归有重要关系。在许多人类癌症中经常观察到该基因的扩增。涉及该基因的易位与人的伯基特淋巴瘤和多发性骨髓瘤有关。它能调控多种与细胞增殖和代谢过程相关基因的表达，并且其对应的基因也是人类癌症中最常见的高丰度癌基因。长非编码核糖核酸在癌症发展和进展中的作用越来越受到重视。特别是，在癌细胞中参与C-MYC和p53通路的lncRNAs的名单正在迅速扩大。MYC能够与MAX形成异二聚体并结合在E-box序列上来激活对应的转录靶标。正是由于MYC在癌症发病机制中的重要作用，发展针对MYC或其通路的抑制剂来调控MYC的表达和活性成为重要研究方向之一。表1.描述人类癌症中MYC与抗肿瘤免疫之间关系的代表性文献。然而，由于直接靶向MYC蛋白的药物极难研发，MYC成为了臭名昭著的“不可成药”靶点，这主要是因为MYC的核定位，缺乏明确的配体结合位点以及大的蛋白质-蛋白质相互作用（PPI）表面。MYC基因在人体组织的表达图2.人类除食管外，在各类分泌腺和免疫相关器官中有较高的表达；小鼠的表达与人类类似，不过最高表达在卵巢和胸腺。（表达信息为归一化的相对值，而非直接RPKM数据；同物种内部比较，小鼠和人之间无可比性）。信息来源：NCBI。推荐文献：1.Hann SR,King MW,Bentley DL,Anderson CW,Eisenman RN(January 1988)."A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas".Cell.52(2):185–95.doi:10.1016/0092-8674(88)90507-7.2.Hiyama T,Haruma K,Kitadai Y,Ito M,Masuda H,Miyamoto M,Tanaka S,Yoshihara M,Sumii K,Shimamoto F,Chayama K(2001)."c-myc gene mutation in gastric mucosa-associated lymphoid tissue(MALT)lymphoma and diffuse large B-cell lymphoma".Oncol.Rep.8(2):289–92.3.Ruf IK,Rhyne PW,Yang H,Borza CM,Hutt-Fletcher LM,Cleveland JL,Sample JT(2001)."EBV regulates c-MYC,apoptosis,and tumorigenicity in Burkitt's lymphoma".Curr.Top.Microbiol.Immunol.Current Topics in Microbiology and Immunology.258:153–60.如果你也对各类动物实验/细胞与基因治疗CRO及技术服务感兴趣，那就快快关注我们的知乎账号：赛业生物cyagen吧！干货高频分享，总有你需要的~还可以关注我们的微信公众号：赛业生物订阅号，针对多类目内容设置了多项趣味专栏，妈妈再也不用担心我找不到资料啦！现在添加小助理微信：cyagen-class，还可以进入交流群共同学习，参与多种福利活动~点赞、推荐、么么哒mua! (*╯3╰)编辑于 2023-02-13 13:46・IP 属地广东核糖核酸（RNA）肿瘤研究方向赞同 464 条评论分享喜欢收藏申请

myc基因_百度百科

因_百度百科网页新闻贴吧知道网盘图片视频地图文库资讯采购百科百度首页登录注册进入词条全站搜索帮助首页秒懂百科特色百科知识专题加入百科百科团队权威合作下载百科APP个人中心收藏查看我的收藏0有用+10myc基因播报讨论上传视频癌基因myc基因是较早发现的一组癌基因，包括C - myc，N -myc，L - myc ，分别定位于8号染色体，2号染色体和1号染色体。结构上由不编码蛋白质的第1外显子和编码蛋白质的第2、3外显子构成，与之同源的病毒癌基因存在于MC29及其它一些具有高度致癌性的猿逆转录病毒中。myc基因高水平表达时可转化啮齿类成纤维细胞。中文名myc基因属性癌基因表现可转化啮齿类成纤维细胞包括C - myc，N -myc，L - myc目录1基本信息2分类和功用3结构及表达4产物及功能5人类肿瘤6临床意义7论文8讨论9结果▪材料▪方法基本信息播报编辑myc基因首次在Burkitt淋巴瘤中发现，可通过染色体易位而活化，最常见的是通过8号染色体与14号染色体间易位，使得8号染色体上的myc基因或其相邻区域与14号染色体的免疫球蛋白重链融合而被活化。myc基因还可以通过染色体2：8或8：22间易位与免疫球蛋白轻链序列融合而被活化。尽管不同肿瘤中影响myc基因的易位断裂点的具体位置可能有所不同，但染色体易位的共通之处是改变了myc基因正常的表达调控机制。除了染色体易位可破坏myc基因的表达调控之外，在某些肿瘤类型中myc基因还受DNA扩增的影响。myc基因在小细胞肺癌中有较高频率扩增，在很多其它类型上皮癌如乳腺癌和结直肠癌中也有扩增。分类和功用播报编辑myc基因包括C - myc，N -myc，L - myc，分别定位于8号染色体，2号染色体和1号染色体。结构上由不编码蛋白质的第1外显子和编码蛋白质的第2，3外显子构成。myc基因属于编码核蛋白的癌基因，3个基因都编码一种与细胞周期调控有关的核内DNA结合蛋白。myc基因家族及其产物可促进细胞增殖，永生化，去分化和转化等，在多种肿瘤形成过程中处于重要地位。myc基因家族中的3个成员对肿瘤形成及在肿瘤类型方面存在差异。认为，C - myc的扩增与肿瘤发生与转归密切相关，N - myc的扩增对肿瘤的预后判断有意义，L - myc扩增与肿瘤的易患性和预后在不同的肿瘤中表现不一样。研究表明，myc基因产物，尤其是c - myc在诱导细胞凋亡过程中也起重要作用。结构及表达播报编辑c-myc基因是禽类髓细胞病毒(AMN)MC-29的V-myc的细胞同源序列，从MC-29病毒中分离的V-myc是gag-myc融合体，它由1358个bp的gag基因与1568个bp的V-myc基因共同组成.C-myc基因由3个外显子及2个内含子组成，第一个外显子不编码，只起调节作用，只有外显子2和3与V-myc相对应，编码一个439个氨基酸的蛋白质.C-myc基因由启动子P1或P2起始转录并在第一内含子中尚有一个潜在启动子P，当第一个内含子发生断裂时，P可被激活而成为一个异常转录起始点，但蛋白合成起始位点不变，并与正常C-myc基因产物相同.在各种不同动物中，C-myc基因和第2.3外显子具有高度保守性，而第1外显子则有较大的差异.小鼠和人的外显子1只有70%的同源性.人类C-myc基因定位于8q24.在生理学上，C-myc基因的表达一般与细胞的生长状态有关，如有生长因子刺激成纤维细胞，可导致C-myc表达增强，相反，在细胞分化时C-myc表达降低，在细胞培养过程中，用C-myc表达结构或反义寡脱氧核酸进行研究，发现C-myc在细胞 G0期到S期的过程中也起作用.表明C-myc表达的变化与细胞的增殖及分化状态有关，其表达产物在调节细胞生长、分化或恶性转化中发挥作用。产物及功能播报编辑C-myc基因的产物为62KD的磷酸化蛋白P62c-mgc，是由C-myc基因的外显子2和3共同编码的由439个氨基酸组成的蛋白质，定位细胞核内，为核蛋白，依C-one编码产物，功能分类，C-myc癌基因属核蛋白基因，具有转化细胞的能力，并具有与染色体 DNA结合的特性，在调节细胞生长、分化及恶性转化中发挥作用.C-Myc蛋白在结构上可分为转录激活区，非特异DNA结合区，核靶序列，碱性区，螺旋一环一螺旋(HLH)及亮氨酸拉链区，在已知的转录因子中可介导蛋白的寡聚化，这两个区同时存在是 C-myc蛋白所特有的，在其它蛋白质中，很少发现.在C-Myc蛋白中，螺旋一环一螺旋紧随着碱性区，揭示其以特异性序列方式和DNA相互作用.在以原核生物为实验对象的研究表明，该碱性区以一个自由环存在，当以特殊方式结合到DNA上时，则变成螺旋，该区是C-Myc蛋白与DNA特异序列的结合部位.在C-Myc中还存在着与抑制细胞分化、自身抑制有关的区域及肿瘤转化所必需的区域.Smith等研究了C-Myc的亮氨酸拉链区，该区介导各种转录因子的二聚作用.在亮氨酸重复部位的突变能显蓍降低C-myc抑制鼠红白血病(MEL)细胞分化能力，同样地，此区的插入突变能消除C-Myc的转化活性.正是这些C-myc结构成分的表达阻止了细胞进入细胞周期，从而抑制许多细胞系的分化.Cronch等对C-Myc亮氨酸拉链区的亮氨酸进行致突变，发现这些突变不能自身抑制，说明了亮氨酸拉链区在自身抑制中的重要性.Stone等研究认为，C-Myc分子的中间1/3以及N-端，C-端是肿瘤转化所必需的，是 C-myc基因与肿瘤转化有关的C-myc区段.正是由于这些C-Myc功能区域的存在，从而使 C-Myc在胞浆内合成后，与其它蛋白形成寡聚体，再转移到核内，并结合到特异性的 DNA序列上，从而激活和抑制许多靶基因的转录，引起细胞生长和分化的改变，发挥其生理调节功能及恶性转化作用.对程序性细胞死亡（Programmed Cell death. PCD）研究的深入，发现Myc蛋白参与诱导细胞凋亡.C-myc基因表达的失调是多种细胞凋亡的主要诱因，细胞发生凋亡的速度及其对诱导因素的敏感性均依赖于细胞Myc蛋白的含量.尚未成熟胸腺细胞中 Myc基因的高表达是胚胎胸腺细胞凋亡坏死的诱因.而且在细胞凋亡阶段，也观察到C-myc基因的高水平表达，如果用反义寡核苷酸阻断C-myc基因的表达，则细胞凋亡受到严重干扰.Evan研究发现，C-myc表达的失调也会启动去除生长因子后培养细胞的成熟前凋亡.他们对小鼠IL-3依赖性髓样细胞素32D进行观察，发现在洗去IL-3后，可立即观察到C-myc基因表达下调.结果使培养细胞停止于G1期，将携带C-myc基因的载体转染32D细胞，获得稳定表达C-myc基因的32D细胞克隆，结果这种细胞去除H-3 后，不停止于G1期，而是启动以凋亡为特征的程序性细胞死亡.结果揭示细胞凋亡是清除定点突变及细胞周期调控失衡的细胞的重要机制，一旦细胞发生障碍，C-myc基因会启动凋零程序，相反，则导致肿瘤形成。人类肿瘤播报编辑myc基因定位于染色体8q24、IgH、IgK、Igλ链的基因位点分别在14q32、2P13和 22q11，在BL细胞中往往出现C-myc基因位点与Ig基因位点之间的易位，即C-myc易位到Ig位点的高活性转录区，从而组成一个高转活性的重排基因，启动C-myc转录，使 C-myc表达增强，促进细胞恶变，最后导致肿瘤的发生.C-myc基因主要通过扩增和染色体易位重排的方式激活，与某些组织肿瘤的发生、发展和演变转归有重要关系.在不同的人体肿瘤细胞系中，包括粒细胞性白血病细胞系，视网膜母细胞瘤细胞系，某些神经母细胞病细胞系，乳腺癌细胞系及某些肺癌细胞系，已发现C-myc或C-myc相关序列的扩增，在人结肠癌细胞系中也观察到 C-myc基因的扩增.C-myc癌基因已在成骨肉瘤、软骨肉瘤、脊索瘤、脂肪肉瘤、横纹肌肉瘤中发现扩增，当扩增达到30倍时，染色体上表现HSR和DMS，而且C-myc过量表达与肿瘤的早期复发有关，在致瘤中，已发现ras与myc、sis与myc、myc与fos偶联激活，协同致瘤等.许多资料表明C-myc位点在所有受检的B细胞肿瘤中有重排，Casares等发现定位在8号染色体上的C-myc与定位在14号染色体上的Ig重链基因有同样的14.2Kb的ecori 酶切片段，因而发生8∶14易位可能是何杰氏淋巴瘤的一个普通标志.N-myc在人神经位母细胞瘤.视网膜母细胞瘤和小细胞肺癌中有扩增，扩增的程度与肿瘤的发病进程有关.Schwab等报告20%的神经母细胞瘤有N-myc扩增，其中大多数是侵袭性肿瘤.Seege r等报告基因拷贝数的多少预示疾病的进程，总的来说，带有一个拷贝数的Ⅰ、Ⅱ、 Ⅲ、Ⅳ.期神经母细胞瘤常规治疗效果较好，带有多个拷贝的Ⅱ、Ⅲ、Ⅳ期病人，病情将不断加重.c-myc首先被发现与小细胞肺癌有关，30%的病例c-myc扩增，复发病人中，myc扩增者的生存期短于没有扩增的病例，研究还发现接受化疗的肿瘤病人易引起myc扩增.有关myc基因扩增与其它肿瘤的关系也有许多报道，认为胃癌、乳腺癌、结肠癌、宫颈癌、何杰金氏病及头部肿瘤等都有myc基因的扩增或过度表达临床意义播报编辑过度表达，见于各种肿瘤，如肺癌，胃癌，乳腺癌，结肠癌，宫颈癌，某些神经母细胞病，粒细胞性白血病，视网膜母细胞瘤，成骨肉瘤，软骨肉瘤，脊索瘤，脂肪肉瘤，横纹肌肉瘤，何杰金氏病及头部肿瘤等都有myc基因的扩增或过度表达。建立同时检测Myc基因3个成员L-myc 、N-myc及C-myc异常扩增的简便方法。方法　采用聚合酶链反应(PCR)技术，用一对引物同时扩增Myc基因3个成员第2外显子中的高度保守区，扩增产物经非变性聚丙烯酰胺凝胶电泳及激光扫描。结果　此法可以检测Myc基因家族中3个成员的扩增情况。经检测，正常组织细胞没有Myc基因扩增，32例喉癌组织中47%有L-myc和C-myc扩增，41%有N-myc 扩增，与正常比差异均有显著意义(χ=6.764,7.609, 5.961;P均<0.05)。C-myc扩增率与用PCR-琼脂糖凝胶电泳检测的结果基本相符(χ=0.254,P>0.05) 。结论　此法对检测肿瘤组织中Myc基因3个成员提供了简易、特异、无放射污染，并且适于临床应用的、优于PCR-琼脂糖凝胶电泳的方法。论文播报编辑Myc基因已被发现了至少3种，C-myc、N-myc和L-myc讨论播报编辑国内外用于检测N-myc、L-myc及C-myc的方法大多采用各种杂交技术。由于应用放射性同位素，需要各种防护措施，不安全又复杂，且一次只能检测Myc基因家族中的一个基因，临床上很难常规应用。PCR－琼脂糖凝胶电泳技术简单、易行、快速，但由于灵敏度低，不能分开只相差3个bpDNA的L-myc和N-myc，所以只能检测C-myc的相对扩增，而不能检测N-myc或L-myc扩增或二者的同时扩增。而且，如果有N-myc或L-myc扩增或二者同时扩增时，即使有C-myc扩增，也会出现假阴性结果。我们首先把PCR技术与中性聚丙烯酰胺凝胶电泳及激光扫描技术结合起来，并用硝酸银试剂使凝胶上的Myc 基因双链染成黑褐色。这样的实验结果特异性高，方法简单，成本低，又避免了放射性同位素的一切弊端，很适合于临床应用。聚丙烯酰胺凝胶电泳分辨率高于琼脂糖凝胶电泳，具备分离只相差一个核苷酸的不同DNA片段的特性。在中性聚丙烯酰胺凝胶中，双链DNA片段的电泳迁移率主要由DNA片段长短决定，而与其碱基组成和顺序基本无关。基于以上原理，我们设计了此实验，目的是能把琼脂糖凝胶电泳上没有分开的只相差3 bp的N-myc和L-myc分开，作到一次可同时检测3种Myc基因的扩增情况。实验表明：用PCR-中性聚丙烯酰胺凝胶电泳和用PCR-琼脂糖凝胶电泳检测C-myc基因结果基本相符，说明本研究建立的方法结果可靠。Myc基因是较早发现的一组癌基因，Myc基因的异常扩增或表达，参与了很多肿瘤的发生和发展。本研究方法对进行3种Myc基因在肿瘤形成过程中作用机理的研究，提供了简便易行的实验手段。结果播报编辑1.PCR-琼脂糖凝胶电泳结果：实验设计的引物扩增Myc 3种基因，经PCR扩增，喉癌组织及正常组织细胞DNA在琼脂糖凝胶上均可见2条小于300 bp 的电泳带。第1条带为N-myc( 230bp)和L-myc(227 bp)2个DNA片段合成带，因两者只相差3 bp，故琼脂糖凝胶电泳不能将其分开而呈现1条带；第2条电泳带为C-myc基因(244 bp)。将电泳结果拍照后的底片在激光扫描仪进行扫描，得出2条带的峰面积值。正常组织细胞的C-myc带比N-myc和L-myc合成带密度弱，比值小于1，求出正常组织细胞的C×(N+L)均值为0.6 。C-myc扩增倍数=喉癌的C×(N+L)×0.6，考虑实验中的综合因素，定为1.5倍以上有C-myc扩增。结果显示：喉癌中有42%的C-myc扩增，正常组织细胞没有C-myc的扩增。2.PCR-中性聚丙烯酰胺凝胶电泳结果：由于中性聚丙烯酰胺凝胶电泳对DNA的分离特性，经PCR扩增后的Myc基因电泳带显示3条。第1条带为L-myc(227 bp)，第2条为N-myc(230 bp)，第3条为C-myc(244 bp) 。将扩增出特异性Myc基因电泳带的凝胶片，直接在激光扫描仪上进行扫描，得出3条带的峰面积值。然后用各自的峰面积值除以各自的碱基数，作为该基因的单拷贝数，将L-myc、N-myc和C-myc三者中最小的单拷贝数设定为1，比较其他2个基因的相对倍数。正常组织细胞L-myc∶N-myc∶C-myc均值为1.0∶2.2∶3.8。结果32例喉癌中47%有L-myc和C-myc的扩增，41%有N-myc扩增。C-myc的扩增率与用PCR-琼脂糖凝胶电泳检测的结果基本一致(χ=0.254，P＞0.614)。材料1.标本：32例喉癌组织取自我院耳鼻咽喉科住院病人，7例正常喉组织取自我科同期住院的非癌症病人，3例正常白细胞取自我院血库人全血。所有标本均经病理证实。根据喉癌组织病理分化程度不同，分为高、中、低分化癌。2.PCR引物：5′-CCCAGCGAGACATCTGGAAGAA-3′，5′-GAGAAGCCGCTCCACATGCAGTC-3′。扩增Myc基因家族的3个基因，即C-myc(244 bp)，N-myc(230 bp)，L-myc(227 bp)，由上海复旦大学遗传学研究所合成。3.试剂：TaqDNA聚合酶、dNTP为Promega公司产品；蛋白酶K为Merke公司产品；硝酸银为沈阳试剂二厂产品；Marker PUC 18质粒DNA HeaⅢ酶切片段为Sigma公司产品。方法1.模板DNA提取：参照参考文献[3]方法进行。2.PCR扩增：PCR扩增总反应体积50 μl，应用模板DNA 50 ng，在DNA扩增仪操作(Perkin Elmer Cetus)，循环周期为94℃1分钟，55℃1分钟，72℃2分钟，经过30个循环后，补加72℃7分钟。3.琼脂糖凝胶电泳步骤：取PCR产物5 μl加1μl上样缓冲液(0.25%溴酚蓝，0.25%二甲苯氰FF，40%蔗糖水溶液)之后备用。制备2%琼脂糖凝胶倒入水平式电泳槽中。待胶凝固后加样，用1×TAE缓冲液作为电极缓冲液，溴化乙锭染色，电压低于5V/cm，时间约为2小时。电泳结束后，凝胶直接在紫外透射仪上观察结果。照像，拍片后的底片在激光扫描仪上进行扫描。4.非变性聚丙烯酰胺凝胶电泳步骤：取PCR产物5 μg加1 μl上样缓冲液之后备用。制备8%非变性聚丙烯酰胺凝胶，灌注于20 cm×20 cm×0. 1 cm垂直板电泳槽中，待凝胶聚合后加样，用1×TBE缓冲液作电极缓冲液，室温下电泳1瓦特约14小时，待指示剂溴酚蓝移到边缘时停止电泳。将电泳后的凝胶移至方盘中进行硝酸银染色。染色过程如下：用双蒸馏水(dH2O)洗凝胶3次后浸泡于染色液(硝酸银1g，加dH2O至500 ml)中30分钟，去掉染色液，用dH2O漂洗3次凝胶，然后浸泡于显色液(NaOH15g，38%甲醛3.8 ml，加dH2O至500ml)中约10分钟，当显出棕黑色DNA区带时，用dH2O洗1次凝胶后，浸于停影液(冰醋酸25 ml，加水至500 ml)中约30分钟，然后把凝胶移至固定液(乙醇25 ml，冰醋酸2.5 ml加dH2O至500 ml)中固定。固定后的凝胶在看片灯上观察结果、拍照片，凝胶直接在激光扫描仪进行扫描。3者在第2外显子中有2个区域高度同源，3个基因分别表达各自独立的蛋白，它们的生理作用基本一致。研究表明，在许多肿瘤细胞中有Myc基因扩增或异常表达，但在不同的肿瘤组织和癌细胞系中，Myc基因家族的成员在扩增或表达方面有些差异。因此，深入研究Myc基因3个成员与人类肿瘤的关系非常有意义。本研究建立的PCR-非变性聚丙烯酰胺凝胶电泳-激光扫描技术，可同时检测肿瘤组织中3种Myc基因的扩增情况，在肿瘤发生发展过程中，为进行3种基因各自作用机理的研究提供了简易的实验手段。新手上路成长任务编辑入门编辑规则本人编辑我有疑问内容质疑在线客服官方贴吧意见反馈投诉建议举报不良信息未通过词条申诉投诉侵权信息封禁查询与解封©2024 Baidu 使用百度前必读 | 百科协议 | 隐私政策 | 百度百科合作平台 | 京ICP证030173号京公网安备110000020000

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Myc 家族介绍人类转录因子 Myc 家族是在发现禽骨髓细胞瘤病毒 (v-Myc) 携带的一个癌基因与常在多种肿瘤中过表达的人类基因细胞 Myc（c-Myc）之间存在同源性后确定的。该家族后来又新增了 n-Myc 和 l-Myc 两种转录因子。c-Myc 的结构c-Myc 是一种分子量为 62 kDa 的蛋白（439 个氨基酸），属于碱性螺旋-环-螺旋拉链 (bHLHZip) 类转录因子。N 端反式激活域 (NTD) 包含转录激活域 (TAD) 及 MBI 和 MBII 两个 MYC 盒，MBI 和 MBII 是参与转录调控和蛋白稳定性的高度保守序列元件 1。c-Myc 的中心部位包含一个核定位信号和另外两个保守的序列元件 MBIII 和 MBIV。C 端结构域包含 bHLHZip 基序，该基序在与另一种 bHLHZip 蛋白—— MAX 发生二聚化之前没有固定的结构。二聚化之后形成有序的 α-螺旋结构，该结构会发生多种翻译后修饰和蛋白质相互作用，可以调控 c-Myc 的功能 1。c-Myc 的功能与调控c-Myc 涉及多种细胞过程，包括增殖、分化、细胞凋亡和代谢 2。c-Myc 和 MAX 的四螺旋结构与 E-box 基序 (5'-CACGTG -3') 等 DNA 序列结合，从而控制特定基因的转录。有报告称，这些基因会参与染色质修饰、DNA 复制以及核糖体和线粒体生物合成。由于 c-Myc 参与了多种细胞功能，因此对其进行严格调控至关重要。c-Myc 的转录受发育或有丝分裂信号的控制。由于 c-Myc 的 mRNA 寿命较短，半衰期只有约 30 分钟，所以如果阳性调节信号减少，c-Myc 蛋白水平会迅速降低 3。c-Myc 还可以被磷酸化，促使蛋白通过泛素蛋白酶体通路降解 4。

c-Myc 与癌症原癌基因 MYC 的失调在人类肿瘤发生过程中具有关键作用。与其他因突变或截短而产生活性的原癌基因不同，MYC 会因失去转录控制而失调，导致蛋白过表达。例如，在人伯基特氏淋巴瘤中，MYC 基因易位至免疫球蛋白重链或轻链位点导致 c-Myc 过表达。在多例人上皮细胞瘤和弥漫大 B 细胞淋巴瘤中也发现了 MYC 基因的扩增，直接与病情的预后差相关联。查看抗内源性 c-Myc 的兔单克隆抗体收听我们对 c-Myc 专家 Gerard Evan 教授的采访c-Myc 磷酸化与降解c-Myc 蛋白在增殖细胞中表达水平较低，且半衰期极短，仅为 30 分钟，之后会通过泛素蛋白酶体途径降解。在血清刺激后，Ras 通过促进 ERK 对 c-Myc 在 Ser 62 上的磷酸化，介导 c-Myc 的稳定化。这样后续会引发 GSK3 对在 Try58 的磷酸化，导致 c-Myc 去稳定化。一旦磷酸化以后，c-Myc 会被 E3 连接酶 Fbw7 和 Skp2 泛素化，导致其蛋白酶体降解。了解用于研究c-Myc 磷酸化的抗体结构与功能c-Myc 蛋白含有非结构化的 N 末端转录调控结构域，该结构域含有保守的 Myc 框 I 至 IV，以及核定位序列。C 末端含有 bHLH-Zip 结构域，这种结构域能保持部分的非结构化直至与 MAX 形成二聚体。一旦 c-Myc 和 MAX 形成异二聚体，它们会通过 E-box 模体 (5'-CACGTG-3') 与 DNA 结合，并通过弯曲 DNA 促进转录。现已发现，c-Myc 的 N 末端结构域能够与 TRRAP、GCN5 和 TBP 等转录因子形成复合物。与 DNA 结合时，异二聚体 Myc-MAX 会召集使染色质修饰复合物聚集，包括组蛋白乙酰基转移酶。亦有发现 Myc 参与了转录抑制，并且在没有 TGF-β缺失的情况下时通过结合并取代解离 Miz-1 辅因子来抑制 CDK2NB (p15INK4b)。c-Myc 也能通过激活 miRNA 簇miR17-92进而抑制基因表达，MiR17-92的激活介导了 E2F1 衰减并靶向到 TGF-β 信号通路。用我们的Fireplex™微胶技术同时分析多种由c-Myc 调控的 miRNA查看用于研究 Myc 表达、调控和靶基因的全部工具参考文献1. Sammak, S. et al. Crystal Structures and Nuclear Magnetic Resonance Studies of the Apo Form of the c-MYC:MAX bHLHZip Complex Reveal a Helical Basic Region in the Absence of DNA. Biochemistry 58, 3144-3154 (2019).2. Stoelzle, T., Schwarb, P., Trumpp, A. & Hynes, N. c-Myc affects mRNA translation, cell proliferation and progenitor cell function in the mammary gland. BMC Biology 7, 63 (2009).3. Kato, G. & Dang, C. Function of the c‐Myc oncoprotein. The FASEB Journal 6, 3065-3072 (1992).4. Miller, D., Thomas, S., Islam, A., Muench, D. & Sedoris, K. c-Myc and Cancer Metabolism. Clinical Cancer Research 18, 5546-5553 (2012).

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Cell Death Discov 综述︱安徽医科大学谷皓团队发表MYC对肿瘤免疫和免疫治疗影响研究综述 - 知乎

Cell Death Discov 综述︱安徽医科大学谷皓团队发表MYC对肿瘤免疫和免疫治疗影响研究综述 - 知乎首发于岚翰生命科学（中文阅读）切换模式写文章登录/注册Cell Death Discov 综述︱安徽医科大学谷皓团队发表MYC对肿瘤免疫和免疫治疗影响研究综述逻辑神经科学以逻辑之学术思维，探索神经科学之奥秘撰文︱李家劲，吴朕，谷皓责编︱方以一，王思珍MYC是第一个在肿瘤细胞中被发现扩增的原癌基因，其异常表达参与了肿瘤进展的相关过程。早在1981年，科学家就首次提出病毒启动子的整合可以驱动细胞MYC的表达并导致癌症，而MYC于1982年首次在人类伯基特淋巴瘤中被发现。从那时起，MYC就成为了肿瘤研究领域的热门基因，迄今为止，对这种癌基因的研究仍在进行。从对MYC转录因子功能的研究，到对MYC的转录靶标进行分析，再到对MYC在肿瘤模型中一系列作用的探索，以及当前热点的肿瘤免疫和免疫治疗研究使科学家们逐渐揭开了MYC，特别是其在肿瘤免疫过程中的神秘面纱。癌基因MYC在多种人类癌症中失调，并作为众多癌症相关信号通路的关键汇聚点，在肿瘤及其免疫微环境中发挥着至关重要的作用。2023年3月25日，安徽医科大学谷皓团队在《细胞死亡发现（Cell Death Discovery）》上发表了题为《MYC对肿瘤免疫和免疫治疗的影响（The effects of MYC on tumor immunity and immunotherapy）》的综述文章。安徽医科大学临床医学“5+3”一体化儿科学专业本科生李家劲和董婷玉为共同第一作者，基础医学院谷皓教授为通讯作者，第一临床医学院临床医学专业本科生吴朕和临床医学“5+3”一体化专业本科生朱达诚参与发表。作者从MYC对肿瘤微环境中多种细胞的调控、MYC介导肿瘤细胞与免疫细胞的联系和靶向MYC的肿瘤免疫治疗三个角度分析了MYC在肿瘤免疫中的关键作用，并对以MYC及其相关信号通路为靶点的肿瘤免疫治疗策略进行了展望。一、MYC基因简介Myc基因家族包括三个成员：MYC、MYCN和MYCL[1]。作为Myc家族的一员，MYC是一种重要的原癌基因，它可以作为转录调节因子在多种人类肿瘤中表达。MYC基因定位于人类8号染色体，其羧基末端包含b-HLH-Zip结构域，该结构域与MYC相关因子X（MAX）结合；这些结构域可以与基因启动子上的E盒（E-box）结合并启动相应基因的转录。MYC的靶基因调控广泛的生物学功能，包括细胞增殖、分化和免疫监视等[1]。因此， MYC信号通路被认为是癌症治疗的潜在靶点。此外，越来越多的证据表明MYC过度激活可以在多个水平上介导肿瘤的免疫抑制[2]。尽管MYC相关的免疫疗法面临诸多挑战，但近年来持续的重大突破使科学家对靶向MYC治疗癌症有了坚定的信心。毫无疑问，深入了解MYC基因家族在肿瘤免疫中的作用和机制，对于开发有效的癌症治疗方法至关重要。二、MYC驱动的肿瘤免疫抑制肿瘤微环境的组成主要包括肿瘤细胞、肿瘤浸润免疫细胞、平滑肌细胞、内皮细胞和癌相关基质细胞等[3]。肿瘤细胞中的MYC依赖性途径可以间接影响细胞因子在肿瘤微环境中的表达。在肿瘤细胞中，其他信号通路通常与MYC相互作用，为肿瘤进展提供强有力的支持，尤其是WNT/β-catenin[4]。在免疫细胞中，MYC抑制先天和适应性免疫反应。先天性免疫细胞亚群MYC的过度激活会抑制促炎介质的产生。适应性免疫细胞亚群MYC的过度激活主要通过抑制效应T细胞降低对肿瘤的杀伤作用。在癌相关成纤维细胞(CAFs)中，MYC可以被CAFs中的一些细胞因子激活，从而抑制肿瘤免疫。此外，CAFs可能以旁分泌方式发出信号，以增强肿瘤中MYC的表达，从而驱动肿瘤发生。图1. MYC在肿瘤微环境中的功能和机制（图源：Li et al., Cell Death Discovery, 2023）三、MYC介导肿瘤细胞与免疫细胞相互作用MYC的过度激活通过肿瘤细胞与不同免疫细胞亚群之间的联系启动肿瘤诱导的免疫抑制。CD8 +T 细胞对于抗肿瘤免疫的建立至关重要，典型的 BRG1/BRM 相关因子 (cBAF) 和 MYC 在活化的 CD8 +T细胞的第一次分裂过程中经常不对称地与两个子细胞共同结合。具有高 MYC 和高 cBAF 的子细胞显示出朝向T(eff) 细胞的细胞命运轨迹[5]。此外，现有研究表明，MYC 是协调 Treg 积累、过渡激活和代谢编程的核心[6]。肿瘤浸润性 B 淋巴细胞 (TIB) 存在于癌症的各个阶段并参与塑造肿瘤的发展。一方面，一些研究表明 TIB 可以诱导和维持抗肿瘤活性。另一方面，也有研究者发现B细胞可能起到促瘤作用。在多种癌症中，肿瘤细胞中激活的 MYC介导避免 NK 细胞的细胞毒性[7]。MYC 是与树突状细胞发育、分化、成熟和代谢的重要转录因子。MYC 在急性髓性白血病和慢性淋巴细胞白血病中过表达，并且能够抑制生物钟基因 Period2的表达，该基因在中性粒细胞中高度表达，从而增强抗肿瘤增殖[8]。图2. MYC在肿瘤微环境中引起免疫抑制（图源：Li et al., Cell Death Discovery, 2023）四、靶向MYC的肿瘤免疫治疗许多潜在的策略已经被开发用于直接或间接抑制 MYC 蛋白的化合物，但 MYC没有明显的小分子结合口袋[9]。现有的直接靶向肿瘤中MYC的治疗策略主要包括使用BET抑制剂阻断MYC和MAX之间的相互作用，以及稳定MYC启动子中的G-四链体（G4）基序[10]。虽然一些BET抑制剂已进入临床试验，但大多数MYC-MAX抑制剂尚未进入。MYC G4元件在开发具有高特异性和亲和力的荧光探针方面具有重要用途。间接MYC治疗策略包括调节与MYC相关的信号分子的活性，从而削弱其在肿瘤中的表达。与直接靶向MYC治疗相比，尽管许多MYC的间接抑制剂已经在临床试验中进行了测试，但耐药性等问题仍需解决。MYC联合免疫疗法主要包括联合封锁 MYC 和免疫检查点，联合 MYC 抑制剂和 CAR-T、MYC 抑制剂和 MYC 激动剂的组合，已显示出强大的治疗潜力，可以通过不同途径和渠道更充分地抑制和调节肿瘤的生长。图3. 靶向MYC的肿瘤免疫治疗（图源：Li et al., Cell Death Discovery, 2023）五、总结与展望综上所述，大多数人类癌症都有MYC的异常表达而影响肿瘤及其免疫，所以研究和开发作用于MYC的药物是有益的。迄今为止，靶向MYC的免疫治疗策略主要包括抑制MYC的翻译，降低肿瘤中MYC mRNA的稳定性，以及直接或间接抑制MYC活性。此外，为了研究各种癌症的治疗策略并克服肿瘤异质性，研究人员现在正试图建立联合免疫疗法，并在许多早期临床试验中显示出令人鼓舞的结果。尽管科学家们已经取得了巨大的成果，但临床结果还需要进一步验证。总之，针对MYC的治疗策略有助于肿瘤免疫的有机恢复，为癌症免疫治疗提供了新的途径。原文链接：https://doi.org/10.1038/s41420-023-01403-3第一作者：李家劲（左）；董婷玉（中）；通讯作者：谷皓（右）（照片提供自：谷皓团队）转载须知：“岚翰生命科学”特邀稿件，本内容著作权归作者和“岚翰生命科学”共同所有，欢迎个人转发分享，未经授权禁止转载，违者必究。参考文献（上下滑动查看） 1. Dang CV: MYC on the path to cancer. Cell 2012, 149(1):22-35.2. Casey SC, Tong L, Li Y, Do R, Walz S, Fitzgerald KN, Gouw AM, Baylot V, Gutgemann I, Eilers M et al: MYC regulates the antitumor immune response through CD47 and PD-L1. Science 2016, 352(6282):227-231.3. Azizi E, Carr AJ, Plitas G, Cornish AE, Konopacki C, Prabhakaran S, Nainys J, Wu K, Kiseliovas V, Setty M et al: Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment. Cell 2018, 174(5):1293-1308 e1236.4. Bisso A, Filipuzzi M, Gamarra Figueroa GP, Brumana G, Biagioni F, Doni M, Ceccotti G, Tanaskovic N, Morelli MJ, Pendino V et al: Cooperation Between MYC and beta-Catenin in Liver Tumorigenesis Requires Yap/Taz. Hepatology 2020, 72(4):1430-1443.5. Guo A, Huang H, Zhu Z, Chen MJ, Shi H, Yuan S, Sharma P, Connelly JP, Liedmann S, Dhungana Y et al: cBAF complex components and MYC cooperate early in CD8(+) T cell fate. Nature 2022, 607(7917):135-141.6. Liston A, Gray DH: Homeostatic control of regulatory T cell diversity. Nat Rev Immunol 2014, 14(3):154-165.7. Cozar B, Greppi M, Carpentier S, Narni-Mancinelli E, Chiossone L, Vivier E: Tumor-Infiltrating Natural Killer Cells. Cancer Discov 2021, 11(1):34-44.8. Wang N, Mi M, Wei X, Sun C: Circadian clock gene Period2 suppresses human chronic myeloid leukemia cell proliferation. Exp Ther Med 2020, 20(6):147.9. Dhanasekaran R, Deutzmann A, Mahauad-Fernandez WD, Hansen AS, Gouw AM, Felsher DW: The MYC oncogene - the grand orchestrator of cancer growth and immune evasion. Nat Rev Clin Oncol 2022, 19(1):23-36.10. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I et al: Selective inhibition of BET bromodomains. Nature 2010, 468(7327):1067-1073.编辑︱杨彬薇本文完发布于 2023-04-08 12:35・IP 属地上海免疫治疗安徽医科大学癌症免疫疗法赞同 31 条评论分享喜欢收藏申请转载文章被以下专栏收录岚翰生命科学（中文阅读）关爱生命科学，报道最新进展；立思维，学知识，

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信号通路及IL-6、JAK2、STAT3、c-Fos和c-Myc背景介绍什么是信号通路？IL-6功能及信号通路是怎样的？JAK2功能及信号通路是怎样的？STAT3功能及信号通路是怎样的？c-Fos功能及信号通路是怎样的？c-Myc功能及信号通路是怎样的？有图片可以展示IL-6、JAK2、STAT3、c-Fos和c-Myc的定位情况吗？IL-6、JAK2、STAT3、c-Fos和c-Myc实验关键点解析IL-6信号检测不到怎么办？会不会是分泌到胞外了？在WB实验中的注意事项有哪些？（来源于某医院客户提问）JAK2蛋白磷酸化修饰形式总是检测不到？在WB实验中的注意事项有哪些？（来源于赣南医学院某客户提问）在WB实验中对STAT3信号通路进行检测，需要特别关注哪些实验关键点？（来源于南昌大学某客户提问）在进行WB检测时，为什么c-Fos有时检测不到条带，有时会检测到多条条带？（来源于国内某高校客户提问）内源的c-Myc抗体是否能够检测Myc标签蛋白？（来源于南昌大学某客户提问）临床客户样本中经常检测不到c-Myc的表达，进行WB时需要特别关注哪些实验关键点？（来源于某生物科技公司客户提问）1. 什么是信号通路？信号通路是指当细胞里要发生某种反应时，信号从细胞外到细胞内传递了一种信息，细胞要根据这种信息来做出反应的现象。信号通路（signal pathway）的提出最早可以追溯到1972年，不过那时被称为信号转换（signal transmission）。1980年，M. Rodbell在一篇综述中提到信号转导（signal transduction），此后这个概念就被广泛使用了。信号通路是指能将细胞外的分子信号经细胞膜传入细胞内发挥效应的一系列酶促反应通路。这些细胞外的分子信号（称为配体，ligand）包括激素、生长因子、细胞因子、神经递质以及其它小分子化合物等。很多信号通路之间存在复杂的互作调控网络，精细调控许多生物过程。肿瘤是世界范围内影响人类健康的主要疾病。信号通路中关键蛋白活性的抑制或过度激活在肿瘤发生发展中扮演了重要的角色。在此基础上这些信号通路的关键蛋白，长期以来被认为是肿瘤生物治疗的潜在靶点。例如原癌基因c-Myc与c-Fos，在增殖和分化等多种细胞过程中发挥调节作用。当他们异常表达时，其调控的相应信号通路与肿瘤的发生有关。这些与肿瘤发生发展密切的信号通路，包括MAPK-ERK Pathway、JAK-STAT Pathway和Myc Pathway等等。

图1 癌症细胞代谢示意图

图2 肿瘤微环境与免疫系统示意图2. IL-6功能及信号通路是怎样的？IL-6可以协同调控 B 细胞分化、浆细胞发生以及急性期反应。IL-6是一个在免疫、组织再生和新陈代谢方面具有多种生物学功能的细胞因子。IL-6是急性期反应的有效诱导因子。在感染和组织损伤期间，IL-6的快速生成有助于宿主防御；但IL-6异常表达与炎症相关癌症和代谢疾病相关。IL-6参与诱导许多淋巴细胞的增殖或分化，如B细胞、胸腺细胞和T细胞等。IL-6参与代谢调控，在肌肉收缩后释放到血液中，从而增加脂解作用并改善胰岛素抵抗。IL-6/JAK/STAT3 通路在许多类型的癌症中异常过度激活。在肿瘤微环境中，IL-6/JAK/STAT3信号通路驱动肿瘤细胞的增殖、存活、侵袭和转移，同时强烈抑制抗肿瘤免疫反应。IL-6表达升高会导致JAK/STAT3 信号传导的过度激活，通常与肿瘤患者预后不良有关。编码JAK酶的基因，特别是JAK2，在骨髓增生性肿瘤中经常发生突变，导致JAK/STAT3 信号传导的组成型激活。STAT3可视为一种致癌基因，在许多肿瘤中过度激活，并且与预后不良有关。

图3 JAK/STAT Signaling: IL-6 Receptor Family Signaling3. JAK2功能及信号通路是怎样的？JAK2作为非受体酪氨酸激酶，参与细胞周期进程、凋亡、有丝分裂重组、遗传不稳定性和组蛋白修饰等过程。JAK2在细胞质中，通过配体结合一定数量的相关细胞因子受体而被激活，在信号转导中发挥关键作用。受体包括生长激素(GHR)、催乳素(PRLR)、瘦素(LEPR)、促红细胞生成素(EPOR)、血小板生成素(THPO) 等I型受体；或干扰素α、干扰素β、干扰素γ和多种白细胞介素等II型受体。JAK2配体与细胞表面受体结合，JAK2发生自磷酸化并磷酸化相关的受体，从而为信号转导蛋白（如STATs蛋白）提供多个结合位点。JAK/STAT信号通路是近年来发现的与细胞因子密切相关的信号通路，参与了细胞的增值、分化、凋亡以及免疫调节等重要生物学过程。JAK激酶家族包括4个成员，即JAK1、JAK2、JAK3和TYK2；STAT家族包括7个成员：STAT1、STAT2、STAT3、STAT4、STA-T5a、STAT5b和STAT6b。由于JAK2/STAT3信号传导能够促进肿瘤增殖、存活、血管生成和肿瘤代谢，并同时抑制抗肿瘤免疫。因此IL-6/JAK2/STAT3信号通路，在抑制肿瘤生长和恢复抗肿瘤免疫方面具有相当大的潜力。4. STAT3功能及信号通路是怎样的？STAT3是一种信号转导和转录激活子，参与调控细胞生长、分化、调亡等多种生物学过程。STAT3介导细胞对白介素、KITLG/SCF、LEP和其他生长因子的反应。一旦被激活，会将共激活剂（例如NCOA1或MED1）募集到目标基因的启动子区域。STAT3可能介导对活化的FGFR1，FGFR2，FGFR3和FGFR4的细胞反应。STAT3可以与各种急性期蛋白基因启动子中的IL6反应元件结合。STAT3通过诱导G1期到S期进程的关键基因的表达参与细胞周期调控，如CCND1。STAT3在LEP激活下可能通过反式激活BIRC5表达发挥凋亡作用。STAT3作为众多致癌信号通路的汇聚点，在调节抗肿瘤免疫反应中发挥着核心作用。IL-6是最经典的STAT3激活剂。IL-6通过与细胞表面的受体结合，从而激活JAK。活化的JAK募集并激活细胞胞质中的STAT3，活化的STAT3二聚化并易位至细胞核，发挥转录调控作用。在正常细胞中，STAT3的瞬时激活将转录信号从质膜上的细胞因子和生长因子受体传递到细胞核。STAT3在大多数人类癌症中变得过度活化，并且通常与不良临床预后有关。因此，STAT3信号通路因其在肿瘤形成、转移和耐药性中的作用而被认为是癌症的潜在治疗靶点。5. c-Fos功能及信号通路是怎样的？c-Fos作为最常见的原癌基因之一，参与多个基因的转录调控。能够调控细胞的生长、分化及传递细胞内信号，在多种生物活动中发挥重要作用。c-Fos是一种核磷蛋白，与c-Jun形成异二聚体，而后形成AP-1（激活蛋白-1）复合物，该复合物与目标基因启动子和增强子区域AP-1特定位点处的DNA结合，将细胞外信号转化为基因表达的变化。c-Fos的表达可由各种胞外刺激快速且瞬间诱导，这些刺激包括生长因子、细胞因子、神经递质、多肽激素和应激反应等。c-Fos在刺激后的瞬时表达持续时间很短，蛋白水平在几小时后便可能消失。MAPK-ERK信号通路在细胞的生长、增殖、分化、转化、凋亡、血管生成等多种生理及病理过程中发挥着重要作用（图4）。多种促有丝分裂因子、分化刺激因子和细胞因子可激活ERK1和ERK2。激活的ERK可以磷酸化c-Fos、c-Jun等转录因子，从而在细胞增殖和分化调节中起直接作用。许多人类的肿瘤组织中都可发现MAPK-ERK信号通路处于异常高表达及高活性状态，促进肿瘤细胞增殖、分化、迁移和血管生成。

图4 MAPK-ERK信号通路6. c-Myc功能及信号通路是怎样的？c-Myc作为最常见的原癌基因，是一种作用广泛的转录调节因子。c-Myc可以在增殖、分化和凋亡等多种细胞过程中发挥调节作用。同家族成员还包括v-Myc、n-Myc和l-Myc。c-Myc的表达在肿瘤中经常上调。通常认为c-Myc激活能够诱导人类肿瘤的发生，所以严格调控c-Myc至关重要。c-Myc的表达由有丝分裂信号诱导并由生长抑制信号抑制。c-Myc的主要调节作用是通过与Max蛋白结合发生的。c-Myc作为体细胞重编程的调控因子，与Sox2、Oct4和KLF4一起调控已分化的细胞重新编程为胚胎样状态。原癌基因作为细胞代谢和增殖的主调节器，与许多促进生长分化的的信号通路相关（图）。通过与其它因子相互作用，调节靶基因的转录激活或转录抑制，从而实现对细胞增殖、分化、凋亡以及代谢的调节。的失调在人类肿瘤发生过程中具有关键作用。与其他基因突变或截短而产生活性的原癌基因不同，会因失去转录控制而失调，导致蛋白过表达。过表达能够诱导癌细胞增殖、阻止分化、促进自我更新和扰乱蛋白质的合成，以及引发肿瘤细胞的免疫逃逸等。点击链接获得更多c-Myc相关内容。结构、功能和调控概览

图5 Myc调节细胞生长和增殖示意图（Chi V Dang., 2012）7. 有图片可以展示IL-6、JAK2、STAT3、c-Fos和c-Myc的定位情况吗？IL-6属于分泌型蛋白，如图6。JAK2定位于细胞核、内膜系统，如图7。STAT3未刺激时主要位于细胞质中，刺激后异位至细胞核，如图8。c-Fos主要定位于细胞核，如图9。c-Fos在静止细胞中以非常低的水平表达于细胞质；当细胞被刺激重新进入生长阶段，会经历两波c-Fos的表达。第一波蛋白表达在FBS诱导7.5min后到达峰值，定位于内质网。第二波蛋白表达发生在诱导20min后，并在1h左右达到峰值，定位于细胞核。c-Myc定位于细胞核，如图10。

图6：IL-6蛋白ICC实验结果图，Anti-IL-6抗体 [EPR20653] (ab214429)。绿色：IL-6，红色：Tubulin，蓝色：DAPI处理条件：脂多糖（LPS）(0.5µg/ml 24小时)和Brefeldin A（BFA）(300 ng/ml 20小时)处理的HUVEC（人脐静脉内皮细胞系）

图7： JAK2蛋白ICC实验结果图，Anti-JAK2 (phospho Y1007 + Y1008) 抗体 [E132] (ab32101)，Anti-JAK2抗体[EPR108(2)] (ab108596)。绿色：JAK2，红色：Tubulin，蓝色：DAPI

图8：STAT3蛋白ICC实验结果图，Anti-STAT3 抗体 [E121-21] (ab32500)。绿色：STAT3，红色：Tubulin，蓝色：DAPI

图9：c-Fos蛋白ICC实验结果图，Anti-c-Fos antibody [EPR21930-238] (ab222699)。绿色：c-Fos，红色：Tubulin，蓝色：DAPI

图10：c-Myc蛋白 ICC实验结果图，Anti-c-Myc 抗体 [Y69] (ab32072)。绿色：c-Myc，红色：Tubulin，蓝色：DAPI1. IL-6信号检测不到怎么办？会不会是分泌到胞外了？在WB实验中的注意事项有哪些？（来源于某医院客户提问）WB小妙招：通常需要在单核细胞或分化的巨噬细胞中检测IL-6。需要特别注意的是，样本通常需要诱导（如LPS、BFA、IL-1ß）才能检测到IL-6，请根据产品说明书选择最合适的处理条件（图11）。IL-6属于分泌型蛋白，建议使用抑制分泌试剂（例如Brefeldin A）处理细胞，抑制IL-1β分泌到细胞外。未处理的样本可作为阴性对照。并且建议设置阳性对照，以确认实验体系没有问题。靶标蛋白在不同样本中的翻译后修饰存在区别，所以实际检测到的条带大小在21 – 28 kDa之间，可能与预测值24 kDa不符。

图11：WB- Anti-IL-6抗体 [EPR20653] (ab214429)。泳道1：30 µg BFA（5ug/ml，4h）处理的A549全细胞裂解液泳道2：30 µg IL-1ß （20 ng/ml，24h）和BFA（5ug/ml，最后4h）处理的A549全细胞裂解液泳道3：30 µg BFA（5ug/ml，4h）处理的IL-6敲除的A549全细胞裂解液泳道4：30 µg IL-1ß （20 ng/ml，24h）和BFA（5ug/ml，最后4h）处理的IL-6敲除的A549全细胞裂解液结果描述：IL-6（绿色），Tubulin（红色）预测条带大小：23 kDa检测条带大小：25 kDa非特异性条带：35 kDa在实验中除了需要注意常规问题外，还要特别关注以下关键控制点：样本制备：添加复合蛋白酶抑制剂以避免靶标蛋白降解。整个样本制备过程中，保持样本置于冰上。通过Bradford分析、Lowry分析或BCA分析测定样本总蛋白浓度。电泳：至少上样20μg总蛋白进行电泳。对于分子量较小的靶标蛋白，请使用15%的分离胶进行电泳。转膜：建议转膜完成后使用丽春红染色，确定转膜是否成功。对于分子量较小的靶标蛋白，建议使用0.22μm的PVDF膜。抗体孵育：请根据产品说明书选择合适的抗体工作浓度。2. JAK2蛋白磷酸化修饰形式总是检测不到？在WB实验中的注意事项有哪些？（来源于赣南医学院某客户提问）WB小妙招：JAK2作为非受体酪氨酸激酶，存在多个磷酸化修饰位点，所以请根据实验需求挑选合适的磷酸化抗体。未处理的样本（eg：细胞/脑组织）较难检测到Y1007 + Y1008磷酸化的JAK2蛋白，建议使用Pervanadate进行预刺激处理（图12和13）。推荐根据JAK2蛋白修饰不同，使用合适的阳性对照。JAK2蛋白的预测分子量约为130kDa，因此在电泳和转膜过程中，请根据大蛋白实验注意事项进行操作。

图12：WB- JAK2 (phospho Y1007 + Y1008) 抗体 [E132] (ab32101)泳道1：10 µg Jurkat全细胞裂解液泳道2：10 µg使用50mM Pervanadate处理5分钟的Jurkat全细胞裂解液泳道3：10 µg使用50mM Pervanadate处理5分钟后加入Alkaline磷酸酶的Jurkat全细胞裂解液

图13：WB- JAK2 (phospho Y1007 + Y1008) 抗体 [E132] (ab32101)泳道1：15 µg 小鼠海马裂解液泳道2：15 µg 小鼠P240海马裂解液泳道3：15 µg 小鼠P7海马裂解液泳道4：15 µg 大鼠海马裂解液泳道5：15 µg 大鼠P7海马裂解液泳道6：15 µg 大鼠大脑皮层裂解液泳道7：15 µg 人类大脑裂解液泳道8：15 µg 小鼠大脑裂解液泳道9：15 µg 大鼠大脑裂解液泳道10：15 µg C6（大鼠胶质肿瘤胶质细胞）全细胞裂解液泳道11：15 µg 使用50mM Pervanadate 处理 5 分钟的C6全细胞裂解液在实验中除了需要注意常规问题外，还要特别关注以下关键控制点：样本制备：添加复合蛋白酶抑制剂以避免靶标蛋白降解。对于磷酸化修饰蛋白添加复合磷酸酶抑制剂，以防止蛋白在提取时被去磷酸化。整个样本制备过程中，保持样本置于冰上。通过Bradford分析、Lowry分析或BCA分析测定样本总蛋白浓度。建议使用阳性对照。电泳：对于分子量较大的靶标蛋白，建议使用8%浓度的分离胶进行电泳。转膜：建议在转膜缓冲液中加入SDS至终浓度为0.1%。建议使用0.45μm的PVDF膜。建议转膜缓冲液中使用10%甲醇或更低浓度。建议转膜完成后使用丽春红染色，确定转膜是否成功。3. 在WB实验中对STAT3信号通路进行检测，需要特别关注哪些实验关键点？（来源于南昌大学某客户提问）WB小妙招：STAT3蛋白第705位酪氨酸的磷酸化将激活STAT3并使其易位到细胞核。但是在一些样本中pSTAT3 Y705表达很低，使用IL-6/IL-22/EGF/IFN-γ/IFN-α处理可能会提高检测到的信号强度（如血清饥饿过夜，然后用100 ng/ml的IL-6 处理30分钟HepG2全细胞裂解液）。（图14）STAT3作为非受体酪氨酸激酶，存在多个磷酸化修饰位点，所以请根据实验需求挑选合适的抗体。推荐使用新鲜制备的裂解液来检测磷酸化形式的STAT3，最大限度地减少磷酸化STAT3蛋白的降解。一些样本在90kD附近可能检测到STAT3的两条目的条带（图14）。图14：重组Anti-STAT3 (phospho Y705)抗体[EPR23968-52] (ab267373)泳道1：血清饥饿过夜，然后用50 ng/ml IFN- α处理30分钟的野生型HeLa全细胞裂解液泳道2：血清饥饿过夜，然后用50 ng/ml IFN- α处理30分钟的STAT3敲除HeLa全细胞裂解液泳道3：用50 ng/ml IFN- α处理30分钟的Jurkat全细胞裂解液泳道4：血清饥饿过夜，然后用100 ng/ml IL-6处理30分钟的HepG2全细胞裂解液*泳道3-4上的裂解液是新鲜制备的，制备后立即用于WB实验，以最大限度地减少蛋白质降解。4. 在进行WB检测时，为什么c-Fos有时检测不到条带，有时又会检测到多条条带？（来源于国内某高校客户提问）WB小妙招：c-Fos 的本底表达水平比较低，需要进行刺激以在WB实验中进行检测。血清饥饿，然后进行20% FBS处理2小时或200nM PMA处理4小时可以诱导细胞中 c-Fos 表达。刺激后 c-Fos 的表达迅速且短暂，因此刺激完成后立即收样，制备裂解液避免蛋白消失非常重要。刺激或处理的细胞裂解物中可能出现多个条带(50-65 kDa)，分别对应于不同形式的 c-Fos 蛋白（图15）。图15：WB- Anti-c-Fos antibody [2H2] (ab208942)泳道1：血清饥饿培养过夜的HeLa全细胞裂解液泳道2：血清饥饿培养，然后进行20% FBS处理2小时的HeLa全细胞裂解液泳道3：大鼠皮层神经元泳道4：膜去极化缓冲液处理5小时的大鼠皮层神经元预测条带大小：c-Fos-41 kDa（绿色）；GAPDH-37 kDa（红色）*刺激或处理的细胞裂解物中的50-65kDa多条带对应于不同形式的 c-Fos 蛋白5. 内源的c-Myc抗体是否能够检测Myc标签蛋白？（来源于南昌大学某客户提问）c-Myc为内源性蛋白，请区分c-Myc与Myc标签之间的区别。例如，ab32072抗体只能用于内源性c-Myc蛋白的检测，它不能检测Myc标签。点击链接获得更多c-Myc与Myc标签的相关内容。c-Myc 和 Myc 标签的抗体6. 临床客户样本中经常检测不到c-Myc的表达，进行WB时需要特别关注哪些实验关键点？（来源于某生物科技公司客户提问）WB小妙招：c-Myc组织特异性低，不同样本中蛋白的表达量存在差异（图16），有些样本可能会出现弱表达或无表达的情况。请选择合适的实验样本，检测前需要确认靶标蛋白表达量，若表达量较低，建议尝试对实验条件进行优化：比如降低稀释度，增加上样量，使用高敏底物等。当检测不到样本信号时，强烈推荐使用阳性对照，以确认实验体系没有问题。c-Myc存在多种翻译后修饰，常出现实际检测分子量与预测条带大小不符，或者两条条带现象。建议不要裁膜，保留全膜或至少 90kDa以下膜来孵育此抗体。图16：重组Anti-c-Myc抗体[Y69] - ChIP Grade (ab32072)泳道 1： MCF-7（人乳腺癌上皮细胞）全细胞裂解液泳道 2： Raji（人伯基特淋巴瘤 B 淋巴细胞）全细胞裂解液泳道 3： K562（人慢性粒细胞白血病淋巴细胞）全细胞裂解液泳道 4： Jurkat（人 T 细胞白血病 T 淋巴细胞）全细胞裂解液泳道 5： THP-1（人单核细胞白血病单核细胞）全细胞裂解液泳道 6：大鼠脾脏全细胞裂解液泳道 7： L6（大鼠骨骼肌成肌细胞）全细胞裂解液泳道 8： Neuro-2a（小鼠成神经细胞瘤成神经细胞）全细胞裂解液泳道 9： RAW264.7（小鼠 Abelson 鼠白血病病毒诱导的肿瘤巨噬细胞）全细胞裂解液预测条带大小：49 kDa检测条带大小：45、57 kDa参考文献：Jae Hyung Park, Woo Yang Pyun, Hyun Woo Park. Cancer Metabolism: Phenotype, Signaling and Therapeutic Targets. Cells. 2020 Oct 16;9(10):2308.doi: 10.3390/cells9102308.Sailan Zou, Qiyu Tong, Bowen Liu, Wei Huang, Yan Tian, Xianghui Fu. Targeting STAT3 in Cancer Immunotherapy. Mol Cancer. 2020 Sep 24;19(1):145. doi: 10.1186/s12943-020-01258-7.Chi V Dang. MYC on the path to cancer. Cell. 2012 Mar 30;149(1):22-35.doi: 10.1016/j.cell.2012.03.003.Stella Pelengaris, Mike Khan, Gerard Evan. c-MYC: more than just a matter of life and death. Nat Rev Cancer. 2002 Oct;2(10):764-76.doi: 10.1038/nrc904.Alan J Whitmarsh. Regulation of gene transcription by mitogen-activated protein kinase signaling pathways. Biochim Biophys Acta. 2007 Aug;1773(8):1285-98. doi: 10.1016/j.bbamcr.2006.11.011. Epub 2006 Nov 17.Paula Monje, Javier Hernández-Losa, Ruth J Lyons, Maria D Castellone, J Silvio Gutkind. Regulation of the transcriptional activity of c-Fos by ERK. A novel role for the prolyl isomerase PIN1. J Biol Chem. 2005 Oct 21;280(42):35081-4. doi: 10.1074/jbc.C500353200. Epub 2005 Aug 25.Sujin Kang, Toshio Tanaka, Masashi Narazaki, Tadamitsu Kishimoto. Targeting Interleukin-6 Signaling in Clinic. Immunity. 2019 Apr 16;50(4):1007-1023. doi: 10.1016/j.immuni.2019.03.026.Jan Mauer, Jesse L Denson, Jens C Brüning. Versatile functions for IL-6 in metabolism and cancer. Trends Immunol. 2015 Feb;36(2):92-101. doi: 10.1016/j.it.2014.12.008. Epub 2015 Jan 21.Christoph Garbers, Samadhi Aparicio-Siegmund, Stefan Rose-John. The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition. Curr Opin Immunol. 2015 Jun;34:75-82. doi: 10.1016/j.coi.2015.02.008. Epub 2015 Mar 6.Daniel E Johnson, Rachel A O'Keefe, Jennifer R Grandis. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018 Apr;15(4):234-248. doi: 10.1038/nrclinonc.2018.8. Epub 2018 Feb 6.Sailan Zou, Qiyu Tong, Bowen Liu, Wei Huang, Yan Tian, Xianghui Fu. Targeting STAT3 in Cancer Immunotherapy. Mol Cancer. 2020 Sep 24;19(1):145. doi: 10.1186/s12943-020-01258-7.Xiaoyi Hu, Jing Li, Maorong Fu, Xia Zhao, Wei Wang. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021 Nov 26;6(1):402. doi: 10.1038/s41392-021-00791-1.Hua Yu, Drew Pardoll, Richard Jove. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009 Nov;9(11):798-809. doi: 10.1038/nrc2734.M Buchert, C J Burns, M Ernst. Targeting JAK kinase in solid tumors: emerging opportunities and challenges. Oncogene. 2016 Feb 25;35(8):939-51. doi: 10.1038/onc.2015.150. Epub 2015 May 18.Fan Liu, Lan Wang, Fabiana Perna, Stephen D Nimer. Beyond transcription factors: how oncogenic signalling reshapes the epigenetic landscape. Nat Rev Cancer. 2016Jun;16(6):359-72. doi: 10.1038/nrc.2016.41.Hua Yu, Heehyoung Lee, Andreas Herrmann, Ralf Buettner, Richard Jove. Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat Rev Cancer. 2014 Nov;14(11):736-46. doi: 10.1038/nrc3818.

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您可点击此处下载c-Myc (MYC)靶点介绍及实验小贴士pdf文件。

图一：c-Myc靶点蛋白结构。图片来源：SWISS-MODEL。c-Myc靶点介绍蛋白功能蛋白定位异构体 & 翻译后修饰WB实验贴士注意事项阳性对照阴性对照结果示例关键控制点IHC实验贴士注意事项阳性对照结果示例关键控制点参考文献c-Myc靶点介绍蛋白功能 c-Myc是一种作用广泛的转录调节因子，可以在增殖、分化和凋亡等多种细胞过程中发挥调节作用。同家族成员还包括v-Myc、n-Myc和l-Myc。 c-Myc是最常见的原癌基因之一，它的表达在肿瘤中经常上调。通常认为c-Myc激活能够诱导人类肿瘤的发生，所以严格调控c-Myc至关重要。c-Myc的表达由有丝分裂信号诱导并由生长抑制信号抑制。 c-Myc的主要调节作用是通过与Max蛋白结合发生的，Max是一种相对稳定的蛋白质，但c-Myc 会迅速降解，半衰期为20-30分钟。 c-Myc作为体细胞重编程的调控因子，与Sox2、Oct4和KLF4一起调控已分化的细胞重新编程为胚胎样状态。蛋白表达 c-Myc作为一种转录调节因子，组织特异性低，在多种肿瘤细胞中高度表达。蛋白特性不同样本中c-Myc的表达量存在差异，选择合适的样本进行实验非常重要。 c-Myc为内源性蛋白，请区分c-Myc与Myc标签之间的区别。蛋白定位细胞核。图二：c-Myc ICC实验结果图，Anti-c-Myc 抗体 [Y69] (ab32072)。绿色：c-Myc，红色：Tubulin，蓝色：DAPI。异构体 & 翻译后修饰人（P01106）：异构体 1-2：49 kDa （预测）小鼠（P01108）：49 kDa （预测）大鼠（P09416）：49 kDa （预测） c-Myc多个位点存在磷酸化修饰乙酰化修饰泛素化修饰糖基化修饰回到顶部

WB实验贴士注意事项 ab32072抗体只能用于内源性c-Myc蛋白的检测，它不会检测Myc标签。 c-Myc组织特异性低，不同样本中蛋白的表达量存在差异，有些样本可能会出现弱表达或无表达的情况。请选择合适的实验样本，检测前需要确认靶标蛋白表达量，若表达量较低，建议尝试对实验条件进行优化：比如降低稀释度，增加上样量，使用高敏底物等。强烈推荐使用阳性对照，以确认实验体系没有问题。 c-Myc存在多种翻译后修饰，常出现实际检测分子量与预测条带大小不符，或者两条条带现象。阳性对照重组人源c-Myc蛋白(ab169901) Jurkat、HeLa细胞系阴性对照人MYC (c-Myc) knockout HEK-293T cell裂解物(ab263850)结果示例图三：WB-Anti- c-Myc 抗体[Y69] (ab32072)。样品：泳道1：20 µg野生型Jurkat细胞裂解液泳道2：20 µg HeLa细胞裂解液泳道3：20 µg 野生型HEK-293T细胞裂解液泳道4：20 µg MYC敲除的HEK-293T细胞裂解液一抗：Anti- c-Myc 抗体[Y69] (ab32072)，浓度 1/1000 稀释。预测条带大小：49 kDa检测条带大小：57 kDa图四：重组Anti-c-Myc抗体[Y69] - ChIP Grade (ab32072)泳道 1： MCF-7（人乳腺癌上皮细胞）全细胞裂解液泳道 2： Raji（人伯基特淋巴瘤 B 淋巴细胞）全细胞裂解液泳道 3： K562（人慢性粒细胞白血病淋巴细胞）全细胞裂解液泳道 4： Jurkat（人 T 细胞白血病 T 淋巴细胞）全细胞裂解液泳道 5： THP-1（人单核细胞白血病单核细胞）全细胞裂解液泳道 6：大鼠脾脏全细胞裂解液泳道 7： L6（大鼠骨骼肌成肌细胞）全细胞裂解液泳道 8： Neuro-2a（小鼠成神经细胞瘤成神经细胞）全细胞裂解液泳道 9： RAW264.7（小鼠 Abelson 鼠白血病病毒诱导的肿瘤巨噬细胞）全细胞裂解液预测条带大小：49 kDa检测条带大小：45、57 kDa关键控制点在实验中除了需要注意常规问题外，还要特别关注以下关键控制点：样本制备添加复合蛋白酶抑制剂以避免靶标蛋白降解。检测磷酸化c-Myc蛋白，建议在裂解液中添加复合磷酸酶抑制剂。超声破碎处理细胞以富集靶标蛋白。通过Bradford分析、Lowry分析或BCA分析测定样本总蛋白浓度。电泳至少上样20μg总蛋白进行电泳。我们强烈建议您在进行新的WB实验时使用阳性裂解液作为对照。转膜建议不要裁膜，保留全膜或至少 90kDa以下膜来孵育此抗体。 PVDF膜激活完成后充分清洗，完全去除膜上残留甲醇。强烈建议转膜完成后使用丽春红染色，确定转膜是否成功。抗体孵育请根据产品说明书选择合适的抗体工作浓度。建议使用新鲜抗体，不建议抗体重复利用。回到顶部

IHC实验贴士注意事项 c-Myc在不同样本中蛋白的表达量存在差异，有些样本可能会出现弱表达或无表达的情况，请选择合适的实验样本。强烈推荐使用阳性对照，以确认实验体系没有问题。阳性对照人结肠腺癌组织结果示例图五：重组Anti-c-Myc抗体[Y69] - ChIP Grade (ab32072)。样品名称：人结肠腺癌组织关键控制点在实验中除了需要注意常规问题外，还要特别关注以下关键控制点：样本固定样本固定时间取决于组织块大小与组织类型，但对于大多数样本，例如使用4%PFA固定，室温固定18-24小时较为合适。封闭如使用荧光基团偶联的二抗进行实验，推荐使用添加1%的BSA和终浓度为0.3M甘氨酸的封闭液，以淬灭醛基引起的自发荧光。如后续使用HRP结合物进行检测，请使用3%过氧化氢处理切片10分钟以封闭内源性过氧化物酶。抗原修复对石蜡切片进行免疫组化实验时，请根据说明书选择合适的抗原修复液。我们建议使用高压锅进行热诱导抗原修复。可以尝试110℃修复切片15分钟。回到顶部

参考文献Chi V Dang. MYC on the path to cancer. Cell. 2012 Mar 30;149(1):22-35.doi: 10.1016/j.cell.2012.03.003. Renumathy Dhanasekaran, Anja Deutzmann, Wadie D Mahauad-Fernandez, Aida S Hansen, Arvin M Gouw, Dean W Felsher. The MYC oncogene - the grand orchestrator of cancer growth and immune evasion. Nat Rev Clin Oncol. 2022 Jan;19(1):23-36. doi: 10.1038/s41571-021-00549-2. Natalie Meyer, Linda Z Penn. Reflecting on 25 years with MYC. Nat Rev Cancer. 2008 Dec;8(12):976-90. doi: 10.1038/nrc2231. Stephanie C Casey, Ling Tong, Yulin Li, Rachel Do, Susanne Walz, Kelly N Fitzgerald, Arvin M Gouw, Virginie Baylot, Ines Gütgemann, Martin Eilers, Dean W Felsher. MYC regulates the antitumor immune response through CD47 and PD-L1. Science. 2016 Apr 8;352(6282):227-31. doi: 10.1126/science.aac9935. Epub 2016 Mar 10.

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The MYC oncogene — the grand orchestrator of cancer growth and immune evasion | Nature Reviews Clinical Oncology

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nature reviews clinical oncology

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article

Review Article

Published: 10 September 2021

The MYC oncogene — the grand orchestrator of cancer growth and immune evasion

Renumathy Dhanasekaran1, Anja Deutzmann

ORCID: orcid.org/0000-0002-3271-14272, Wadie D. Mahauad-Fernandez2, Aida S. Hansen

ORCID: orcid.org/0000-0002-6547-83932, Arvin M. Gouw2 & …Dean W. Felsher2 Show authors

Nature Reviews Clinical Oncology

volume 19, pages 23–36 (2022)Cite this article

16k Accesses

217 Citations

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Cancer therapyOncogenesOncogenesis

AbstractThe MYC proto-oncogenes encode a family of transcription factors that are among the most commonly activated oncoproteins in human neoplasias. Indeed, MYC aberrations or upregulation of MYC-related pathways by alternate mechanisms occur in the vast majority of cancers. MYC proteins are master regulators of cellular programmes. Thus, cancers with MYC activation elicit many of the hallmarks of cancer required for autonomous neoplastic growth. In preclinical models, MYC inactivation can result in sustained tumour regression, a phenomenon that has been attributed to oncogene addiction. Many therapeutic agents that directly target MYC are under development; however, to date, their clinical efficacy remains to be demonstrated. In the past few years, studies have demonstrated that MYC signalling can enable tumour cells to dysregulate their microenvironment and evade the host immune response. Herein, we discuss how MYC pathways not only dictate cancer cell pathophysiology but also suppress the host immune response against that cancer. We also propose that therapies targeting the MYC pathway will be key to reversing cancerous growth and restoring antitumour immune responses in patients with MYC-driven cancers.Key points

The MYC oncogene is activated in the vast majority of cancers by genetic, epigenetic or post-translational mechanisms.

In preclinical models, inactivation of MYC can result in sustained tumour regression owing to oncogene addiction.

MYC activation drives cancer progression through mechanisms involving either the cell-intrinsic acquisition of hallmarks of cancer or dysregulation of the tumour microenvironment and host immune responses.

MYC leads to cancer initiation and maintenance by regulating the host immune system through mechanisms involving immune checkpoints, specific receptors and secreted cytokines.

Currently, no direct inhibitors of MYC are approved; however, many therapeutic agents targeting MYC are under development.

We propose that therapies targeting the MYC pathway will be key to reversing cancerous growth and restoring antitumour immune responses in patients with MYC-driven cancers.

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Fig. 1: Major genetic alterations involving MYC and its paralogues in human cancers.Fig. 2: Mechanisms leading to MYC activation in human cancers.Fig. 3: MYC is a grand orchestrator of the hallmarks of cancer.Fig. 4: MYC blocks immune surveillance.Fig. 5: Therapeutic strategies to target MYC-driven tumours.Fig. 6: Proposed biomarker-stratified therapeutic strategies to target MYC-driven cancers.

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Download referencesAcknowledgementsR.D. receives grant support from the NIH (grant CA222676). A.D. has received support from Lymphoma Research Foundation. A.S.H. has received support from Lundbreck Foundation. A.M.G. has received support from the NIH (grant CA196585). D.W.F. receives grant support from the NIH (grants CA208735, CA253180, CA188383 and CA184384).Author informationAuthors and AffiliationsDivision of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USARenumathy DhanasekaranDivision of Oncology, Department of Medicine and Department of Pathology, Stanford University School of Medicine, Stanford, CA, USAAnja Deutzmann, Wadie D. Mahauad-Fernandez, Aida S. Hansen, Arvin M. Gouw & Dean W. FelsherAuthorsRenumathy DhanasekaranView author publicationsYou can also search for this author in

PubMed Google ScholarAnja DeutzmannView author publicationsYou can also search for this author in

PubMed Google ScholarWadie D. Mahauad-FernandezView author publicationsYou can also search for this author in

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PubMed Google ScholarContributionsR.D. and D.W.F. researched data for this manuscript. All authors contributed to the discussion of content and preparation of the manuscript.Corresponding authorCorrespondence to

Dean W. Felsher.Ethics declarations

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D.W.F. is a consultant for Revolution Medicines, a company developing MYC pathway therapies, co-founder of Bachus and Molecular Decisions, and has had advisory roles for American Gene Technologies, Geron, Moderna and Regulus. The other authors declare no conflicts of interest.

Additional informationPeer review informationNature Reviews Clinical Oncology thanks M. Eilers, C.M. Eischen, E.V. Prochownik and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.Publisher’s noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplementary InformationRights and permissionsReprints and permissionsAbout this articleCite this articleDhanasekaran, R., Deutzmann, A., Mahauad-Fernandez, W.D. et al. The MYC oncogene — the grand orchestrator of cancer growth and immune evasion.

Nat Rev Clin Oncol 19, 23–36 (2022). https://doi.org/10.1038/s41571-021-00549-2Download citationAccepted: 28 July 2021Published: 10 September 2021Issue Date: January 2022DOI: https://doi.org/10.1038/s41571-021-00549-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard

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myc基因

鎖定

myc基因是較早發現的一組癌基因，包括C - myc，N -myc，L - myc ，分別定位於8號染色體，2號染色體和1號染色體。結構上由不編碼蛋白質的第1外顯子和編碼蛋白質的第2、3外顯子構成，與之同源的病毒癌基因存在於MC29及其它一些具有高度致癌性的猿逆轉錄病毒中。myc基因高水平表達時可轉化齧齒類成纖維細胞。

中文名

myc基因

屬性

癌基因

表現

可轉化齧齒類成纖維細胞

包括

C - myc，N -myc，L - myc

基本信息

分類和功用

結構及表達

產物及功能

人類腫瘤

臨牀意義

論文

討論

結果

▪

材料

▪

方法

myc基因基本信息

myc基因首次在Burkitt淋巴瘤中發現，可通過染色體易位而活化，最常見的是通過8號染色體與14號染色體間易位，使得8號染色體上的myc基因或其相鄰區域與14號染色體的免疫球蛋白重鏈融合而被活化。myc基因還可以通過染色體2：8或8：22間易位與免疫球蛋白輕鏈序列融合而被活化。儘管不同腫瘤中影響myc基因的易位斷裂點的具體位置可能有所不同，但染色體易位的共通之處是改變了myc基因正常的表達調控機制。除了染色體易位可破壞myc基因的表達調控之外，在某些腫瘤類型中myc基因還受DNA擴增的影響。myc基因在小細胞肺癌中有較高頻率擴增，在很多其它類型上皮癌如乳腺癌和結直腸癌中也有擴增。

myc基因分類和功用

myc基因包括C - myc，N -myc，L - myc，分別定位於8號染色體，2號染色體和1號染色體。結構上由不編碼蛋白質的第1外顯子和編碼蛋白質的第2，3外顯子構成。myc基因屬於編碼核蛋白的癌基因，3個基因都編碼一種與細胞週期調控有關的核內DNA結合蛋白。myc基因家族及其產物可促進細胞增殖，永生化，去分化和轉化等，在多種腫瘤形成過程中處於重要地位。myc基因家族中的3個成員對腫瘤形成及在腫瘤類型方面存在差異。認為，C - myc的擴增與腫瘤發生與轉歸密切相關，N - myc的擴增對腫瘤的預後判斷有意義，L - myc擴增與腫瘤的易患性和預後在不同的腫瘤中表現不一樣。研究表明，myc基因產物，尤其是c - myc在誘導細胞凋亡過程中也起重要作用。

myc基因結構及表達

c-myc基因是禽類髓細胞病毒(AMN)MC-29的V-myc的細胞同源序列，從MC-29病毒中分離的V-myc是gag-myc融合體，它由1358個bp的gag基因與1568個bp的V-myc基因共同組成.C-myc基因由3個外顯子及2個內含子組成，第一個外顯子不編碼，只起調節作用，只有外顯子2和3與V-myc相對應，編碼一個439個氨基酸的蛋白質.C-myc基因由啓動子P1或P2起始轉錄並在第一內含子中尚有一個潛在啓動子P，當第一個內含子發生斷裂時，P可被激活而成為一個異常轉錄起始點，但蛋白合成起始位點不變，並與正常C-myc基因產物相同.在各種不同動物中，C-myc基因和第2.3外顯子具有高度保守性，而第1外顯子則有較大的差異.小鼠和人的外顯子1只有70%的同源性.人類C-myc基因定位於8q24.在生理學上，C-myc基因的表達一般與細胞的生長狀態有關，如有生長因子刺激成纖維細胞，可導致C-myc表達增強，相反，在細胞分化時C-myc表達降低，在細胞培養過程中，用C-myc表達結構或反義寡脱氧核酸進行研究，發現C-myc在細胞 G0期到S期的過程中也起作用.表明C-myc表達的變化與細胞的增殖及分化狀態有關，其表達產物在調節細胞生長、分化或惡性轉化中發揮作用。

myc基因產物及功能

C-myc基因的產物為62KD的磷酸化蛋白P62c-mgc，是由C-myc基因的外顯子2和3共同編碼的由439個氨基酸組成的蛋白質，定位細胞核內，為核蛋白，依C-one編碼產物，功能分類，C-myc癌基因屬核蛋白基因，具有轉化細胞的能力，並具有與染色體 DNA結合的特性，在調節細胞生長、分化及惡性轉化中發揮作用.C-Myc蛋白在結構上可分為轉錄激活區，非特異DNA結合區，核靶序列，鹼性區，螺旋一環一螺旋(HLH)及亮氨酸拉鍊區，在已知的轉錄因子中可介導蛋白的寡聚化，這兩個區同時存在是 C-myc蛋白所特有的，在其它蛋白質中，很少發現.在C-Myc蛋白中，螺旋一環一螺旋緊隨着鹼性區，揭示其以特異性序列方式和DNA相互作用.在以原核生物為實驗對象的研究表明，該鹼性區以一個自由環存在，當以特殊方式結合到DNA上時，則變成螺旋，該區是C-Myc蛋白與DNA特異序列的結合部位.在C-Myc中還存在着與抑制細胞分化、自身抑制有關的區域及腫瘤轉化所必需的區域.Smith等研究了C-Myc的亮氨酸拉鍊區，該區介導各種轉錄因子的二聚作用.在亮氨酸重複部位的突變能顯蓍降低C-myc抑制鼠紅白血病(MEL)細胞分化能力，同樣地，此區的插入突變能消除C-Myc的轉化活性.正是這些C-myc結構成分的表達阻止了細胞進入細胞週期，從而抑制許多細胞系的分化.Cronch等對C-Myc亮氨酸拉鍊區的亮氨酸進行致突變，發現這些突變不能自身抑制，説明了亮氨酸拉鍊區在自身抑制中的重要性.Stone等研究認為，C-Myc分子的中間1/3以及N-端，C-端是腫瘤轉化所必需的，是 C-myc基因與腫瘤轉化有關的C-myc區段.正是由於這些C-Myc功能區域的存在，從而使 C-Myc在胞漿內合成後，與其它蛋白形成寡聚體，再轉移到核內，並結合到特異性的 DNA序列上，從而激活和抑制許多靶基因的轉錄，引起細胞生長和分化的改變，發揮其生理調節功能及惡性轉化作用.對程序性細胞死亡（Programmed Cell death. PCD）研究的深入，發現Myc蛋白參與誘導細胞凋亡.C-myc基因表達的失調是多種細胞凋亡的主要誘因，細胞發生凋亡的速度及其對誘導因素的敏感性均依賴於細胞Myc蛋白的含量.尚未成熟胸腺細胞中 Myc基因的高表達是胚胎胸腺細胞凋亡壞死的誘因.而且在細胞凋亡階段，也觀察到C-myc基因的高水平表達，如果用反義寡核苷酸阻斷C-myc基因的表達，則細胞凋亡受到嚴重干擾.Evan研究發現，C-myc表達的失調也會啓動去除生長因子後培養細胞的成熟前凋亡.他們對小鼠IL-3依賴性髓樣細胞素32D進行觀察，發現在洗去IL-3後，可立即觀察到C-myc基因表達下調.結果使培養細胞停止於G1期，將攜帶C-myc基因的載體轉染32D細胞，獲得穩定表達C-myc基因的32D細胞克隆，結果這種細胞去除H-3 後，不停止於G1期，而是啓動以凋亡為特徵的程序性細胞死亡.結果揭示細胞凋亡是清除定點突變及細胞週期調控失衡的細胞的重要機制，一旦細胞發生障礙，C-myc基因會啓動凋零程序，相反，則導致腫瘤形成。

myc基因人類腫瘤

myc基因定位於染色體8q24、IgH、IgK、Igλ鏈的基因位點分別在14q32、2P13和 22q11，在BL細胞中往往出現C-myc基因位點與Ig基因位點之間的易位，即C-myc易位到Ig位點的高活性轉錄區，從而組成一個高轉活性的重排基因，啓動C-myc轉錄，使 C-myc表達增強，促進細胞惡變，最後導致腫瘤的發生.C-myc基因主要通過擴增和染色體易位重排的方式激活，與某些組織腫瘤的發生、發展和演變轉歸有重要關係.在不同的人體腫瘤細胞系中，包括粒細胞性白血病細胞系，視網膜母細胞瘤細胞系，某些神經母細胞病細胞系，乳腺癌細胞系及某些肺癌細胞系，已發現C-myc或C-myc相關序列的擴增，在人結腸癌細胞系中也觀察到 C-myc基因的擴增.C-myc癌基因已在成骨肉瘤、軟骨肉瘤、脊索瘤、脂肪肉瘤、橫紋肌肉瘤中發現擴增，當擴增達到30倍時，染色體上表現HSR和DMS，而且C-myc過量表達與腫瘤的早期復發有關，在致瘤中，已發現ras與myc、sis與myc、myc與fos偶聯激活，協同致瘤等.許多資料表明C-myc位點在所有受檢的B細胞腫瘤中有重排，Casares等發現定位在8號染色體上的C-myc與定位在14號染色體上的Ig重鏈基因有同樣的14.2Kb的ecori 酶切片段，因而發生8∶14易位可能是何傑氏淋巴瘤的一個普通標誌.N-myc在人神經位母細胞瘤.視網膜母細胞瘤和小細胞肺癌中有擴增，擴增的程度與腫瘤的發病進程有關.Schwab等報告20%的神經母細胞瘤有N-myc擴增，其中大多數是侵襲性腫瘤.Seege r等報告基因拷貝數的多少預示疾病的進程，總的來説，帶有一個拷貝數的Ⅰ、Ⅱ、 Ⅲ、Ⅳ.期神經母細胞瘤常規治療效果較好，帶有多個拷貝的Ⅱ、Ⅲ、Ⅳ期病人，病情將不斷加重.c-myc首先被發現與小細胞肺癌有關，30%的病例c-myc擴增，復發病人中，myc擴增者的生存期短於沒有擴增的病例，研究還發現接受化療的腫瘤病人易引起myc擴增.有關myc基因擴增與其它腫瘤的關係也有許多報道，認為胃癌、乳腺癌、結腸癌、宮頸癌、何杰金氏病及頭部腫瘤等都有myc基因的擴增或過度表達

myc基因臨牀意義

過度表達，見於各種腫瘤，如肺癌，胃癌，乳腺癌，結腸癌，宮頸癌，某些神經母細胞病，粒細胞性白血病，視網膜母細胞瘤，成骨肉瘤，軟骨肉瘤，脊索瘤，脂肪肉瘤，橫紋肌肉瘤，何杰金氏病及頭部腫瘤等都有myc基因的擴增或過度表達。建立同時檢測Myc基因3個成員L-myc 、N-myc及C-myc異常擴增的簡便方法。方法　採用聚合酶鏈反應(PCR)技術，用一對引物同時擴增Myc基因3個成員第2外顯子中的高度保守區，擴增產物經非變性聚丙烯酰胺凝膠電泳及激光掃描。結果　此法可以檢測Myc基因家族中3個成員的擴增情況。經檢測，正常組織細胞沒有Myc基因擴增，32例喉癌組織中47%有L-myc和C-myc擴增，41%有N-myc 擴增，與正常比差異均有顯著意義(χ=6.764,7.609, 5.961;P均<0.05)。C-myc擴增率與用PCR-瓊脂糖凝膠電泳檢測的結果基本相符(χ=0.254,P>0.05) 。結論　此法對檢測腫瘤組織中Myc基因3個成員提供了簡易、特異、無放射污染，並且適於臨牀應用的、優於PCR-瓊脂糖凝膠電泳的方法。

myc基因論文

Myc基因已被發現了至少3種，C-myc、N-myc和L-myc

myc基因討論

國內外用於檢測N-myc、L-myc及C-myc的方法大多采用各種雜交技術。由於應用放射性同位素，需要各種防護措施，不安全又複雜，且一次只能檢測Myc基因家族中的一個基因，臨牀上很難常規應用。PCR－瓊脂糖凝膠電泳技術簡單、易行、快速，但由於靈敏度低，不能分開只相差3個bpDNA的L-myc和N-myc，所以只能檢測C-myc的相對擴增，而不能檢測N-myc或L-myc擴增或二者的同時擴增。而且，如果有N-myc或L-myc擴增或二者同時擴增時，即使有C-myc擴增，也會出現假陰性結果。我們首先把PCR技術與中性聚丙烯酰胺凝膠電泳及激光掃描技術結合起來，並用硝酸銀試劑使凝膠上的Myc 基因雙鏈染成黑褐色。這樣的實驗結果特異性高，方法簡單，成本低，又避免了放射性同位素的一切弊端，很適合於臨牀應用。聚丙烯酰胺凝膠電泳分辨率高於瓊脂糖凝膠電泳，具備分離只相差一個核苷酸的不同DNA片段的特性。在中性聚丙烯酰胺凝膠中，雙鏈DNA片段的電泳遷移率主要由DNA片段長短決定，而與其鹼基組成和順序基本無關。基於以上原理，我們設計了此實驗，目的是能把瓊脂糖凝膠電泳上沒有分開的只相差3 bp的N-myc和L-myc分開，作到一次可同時檢測3種Myc基因的擴增情況。實驗表明：用PCR-中性聚丙烯酰胺凝膠電泳和用PCR-瓊脂糖凝膠電泳檢測C-myc基因結果基本相符，説明本研究建立的方法結果可靠。Myc基因是較早發現的一組癌基因，Myc基因的異常擴增或表達，參與了很多腫瘤的發生和發展。本研究方法對進行3種Myc基因在腫瘤形成過程中作用機理的研究，提供了簡便易行的實驗手段。

myc基因結果

1.PCR-瓊脂糖凝膠電泳結果：實驗設計的引物擴增Myc 3種基因，經PCR擴增，喉癌組織及正常組織細胞DNA在瓊脂糖凝膠上均可見2條小於300 bp 的電泳帶。第1條帶為N-myc( 230bp)和L-myc(227 bp)2個DNA片段合成帶，因兩者只相差3 bp，故瓊脂糖凝膠電泳不能將其分開而呈現1條帶；第2條電泳帶為C-myc基因(244 bp)。將電泳結果拍照後的底片在激光掃描儀進行掃描，得出2條帶的峯面積值。正常組織細胞的C-myc帶比N-myc和L-myc合成帶密度弱，比值小於1，求出正常組織細胞的C×(N+L)均值為0.6 。C-myc擴增倍數=喉癌的C×(N+L)×0.6，考慮實驗中的綜合因素，定為1.5倍以上有C-myc擴增。結果顯示：喉癌中有42%的C-myc擴增，正常組織細胞沒有C-myc的擴增。2.PCR-中性聚丙烯酰胺凝膠電泳結果：由於中性聚丙烯酰胺凝膠電泳對DNA的分離特性，經PCR擴增後的Myc基因電泳帶顯示3條。第1條帶為L-myc(227 bp)，第2條為N-myc(230 bp)，第3條為C-myc(244 bp) 。將擴增出特異性Myc基因電泳帶的凝膠片，直接在激光掃描儀上進行掃描，得出3條帶的峯面積值。然後用各自的峯面積值除以各自的鹼基數，作為該基因的單拷貝數，將L-myc、N-myc和C-myc三者中最小的單拷貝數設定為1，比較其他2個基因的相對倍數。正常組織細胞L-myc∶N-myc∶C-myc均值為1.0∶2.2∶3.8。結果32例喉癌中47%有L-myc和C-myc的擴增，41%有N-myc擴增。C-myc的擴增率與用PCR-瓊脂糖凝膠電泳檢測的結果基本一致(χ=0.254，P＞0.614)。

myc基因材料

1.標本：32例喉癌組織取自我院耳鼻咽喉科住院病人，7例正常喉組織取自我科同期住院的非癌症病人，3例正常白細胞取自我院血庫人全血。所有標本均經病理證實。根據喉癌組織病理分化程度不同，分為高、中、低分化癌。2.PCR引物：5′-CCCAGCGAGACATCTGGAAGAA-3′，5′-GAGAAGCCGCTCCACATGCAGTC-3′。擴增Myc基因家族的3個基因，即C-myc(244 bp)，N-myc(230 bp)，L-myc(227 bp)，由上海復旦大學遺傳學研究所合成。3.試劑：TaqDNA聚合酶、dNTP為Promega公司產品；蛋白酶K為Merke公司產品；硝酸銀為瀋陽試劑二廠產品；Marker PUC 18質粒DNA HeaⅢ酶切片段為Sigma公司產品。

myc基因方法

1.模板DNA提取：參照參考文獻[3]方法進行。2.PCR擴增：PCR擴增總反應體積50 μl，應用模板DNA 50 ng，在DNA擴增儀操作(Perkin Elmer Cetus)，循環週期為94℃1分鐘，55℃1分鐘，72℃2分鐘，經過30個循環後，補加72℃7分鐘。3.瓊脂糖凝膠電泳步驟：取PCR產物5 μl加1μl上樣緩衝液(0.25%溴酚藍，0.25%二甲苯氰FF，40%蔗糖水溶液)之後備用。製備2%瓊脂糖凝膠倒入水平式電泳槽中。待膠凝固後加樣，用1×TAE緩衝液作為電極緩衝液，溴化乙錠染色，電壓低於5V/cm，時間約為2小時。電泳結束後，凝膠直接在紫外透射儀上觀察結果。照像，拍片後的底片在激光掃描儀上進行掃描。4.非變性聚丙烯酰胺凝膠電泳步驟：取PCR產物5 μg加1 μl上樣緩衝液之後備用。製備8%非變性聚丙烯酰胺凝膠，灌注於20 cm×20 cm×0. 1 cm垂直板電泳槽中，待凝膠聚合後加樣，用1×TBE緩衝液作電極緩衝液，室温下電泳1瓦特約14小時，待指示劑溴酚藍移到邊緣時停止電泳。將電泳後的凝膠移至方盤中進行硝酸銀染色。染色過程如下：用雙蒸餾水(dH2O)洗凝膠3次後浸泡於染色液(硝酸銀1g，加dH2O至500 ml)中30分鐘，去掉染色液，用dH2O漂洗3次凝膠，然後浸泡於顯色液(NaOH15g，38%甲醛3.8 ml，加dH2O至500ml)中約10分鐘，當顯出棕黑色DNA區帶時，用dH2O洗1次凝膠後，浸於停影液(冰醋酸25 ml，加水至500 ml)中約30分鐘，然後把凝膠移至固定液(乙醇25 ml，冰醋酸2.5 ml加dH2O至500 ml)中固定。固定後的凝膠在看片燈上觀察結果、拍照片，凝膠直接在激光掃描儀進行掃描。3者在第2外顯子中有2個區域高度同源，3個基因分別表達各自獨立的蛋白，它們的生理作用基本一致。研究表明，在許多腫瘤細胞中有Myc基因擴增或異常表達，但在不同的腫瘤組織和癌細胞系中，Myc基因家族的成員在擴增或表達方面有些差異。因此，深入研究Myc基因3個成員與人類腫瘤的關係非常有意義。本研究建立的PCR-非變性聚丙烯酰胺凝膠電泳-激光掃描技術，可同時檢測腫瘤組織中3種Myc基因的擴增情況，在腫瘤發生發展過程中，為進行3種基因各自作用機理的研究提供了簡易的實驗手段。

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MYC protein interactors in gene transcription and cancer | Nature Reviews Cancer

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nature reviews cancer

perspectives

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Perspective

Published: 29 June 2021

MYC protein interactors in gene transcription and cancer

Corey Lourenco1, Diana Resetca1,2 na1, Cornelia Redel

ORCID: orcid.org/0000-0002-3632-33171,2 na1, Peter Lin

ORCID: orcid.org/0000-0003-3710-38741,2, Alannah S. MacDonald1,2, Roberto Ciaccio

ORCID: orcid.org/0000-0003-3024-92053, Tristan M. G. Kenney

ORCID: orcid.org/0000-0001-8242-43491,2, Yong Wei1,4, David W. Andrews2,4, Maria Sunnerhagen5, Cheryl H. Arrowsmith

ORCID: orcid.org/0000-0002-4971-32501,2,6, Brian Raught1,2 & …Linda Z. Penn

ORCID: orcid.org/0000-0001-8133-54591,2 Show authors

Nature Reviews Cancer

volume 21, pages 579–591 (2021)Cite this article

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OncogenesTranscriptional regulatory elements

AbstractThe transcription factor and oncoprotein MYC is a potent driver of many human cancers and can regulate numerous biological activities that contribute to tumorigenesis. How a single transcription factor can regulate such a diverse set of biological programmes is central to the understanding of MYC function in cancer. In this Perspective, we highlight how multiple proteins that interact with MYC enable MYC to regulate several central control points of gene transcription. These include promoter binding, epigenetic modifications, initiation, elongation and post-transcriptional processes. Evidence shows that a combination of multiple protein interactions enables MYC to function as a potent oncoprotein, working together in a ‘coalition model’, as presented here. Moreover, as MYC depends on its protein interactome for function, we discuss recent research that emphasizes an unprecedented opportunity to target protein interactors to directly impede MYC oncogenesis.

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Fig. 1: MYC dysregulation in human cancers.Fig. 2: MYC regulation of gene transcription is dependent on protein interactors.Fig. 3: Structure of the MYC family of transforming oncoproteins.Fig. 4: MYC protein–protein interactions during transcription.Fig. 5: The coalition model: coordinating the MYC interactome to drive oncogenesis.

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Download referencesAcknowledgementsThe authors thank all the members of the Penn laboratory for their feedback and helpful discussions, especially A. Tamachi, who was an important editor and contributor to the structure of the Perspective.Author informationAuthor notesThese authors contributed equally: Diana Resetca, Cornelia Redel.Authors and AffiliationsPrincess Margaret Cancer Centre, Toronto, ON, CanadaCorey Lourenco, Diana Resetca, Cornelia Redel, Peter Lin, Alannah S. MacDonald, Tristan M. G. Kenney, Yong Wei, Cheryl H. Arrowsmith, Brian Raught & Linda Z. PennDepartment of Medical Biophysics, University of Toronto, Toronto, ON, CanadaDiana Resetca, Cornelia Redel, Peter Lin, Alannah S. MacDonald, Tristan M. G. Kenney, David W. Andrews, Cheryl H. Arrowsmith, Brian Raught & Linda Z. PennDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, ItalyRoberto CiaccioBiological Sciences, Sunnybrook Research Institute, Toronto, ON, CanadaYong Wei & David W. AndrewsDepartment of Physics, Chemistry and Biology, Linköping University, Linköping, SwedenMaria SunnerhagenStructural Genomics Consortium, Toronto, ON, CanadaCheryl H. ArrowsmithAuthorsCorey LourencoView author publicationsYou can also search for this author in

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PubMed Google ScholarContributionsC.L., D.R., C.R., P.L., A.S.M., R.C. and T.M.G.K. researched data for the article, substantially contributed to discussion of the content, wrote the article and reviewed or edited the article before submission. Y.W. researched data for the article, substantially contributed to discussion of the content and wrote the article. D.W.A., M.S., C.H.A. and B.R. reviewed or edited the article before submission. L.Z.P. researched data for the article, substantially contributed to discussion of the content and reviewed and edited the article before submission.Corresponding authorCorrespondence to

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Additional informationPeer review informationNature Reviews Cancer thanks E. Prochownik, L. Soucek and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.Publisher’s noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Rights and permissionsReprints and permissionsAbout this articleCite this articleLourenco, C., Resetca, D., Redel, C. et al. MYC protein interactors in gene transcription and cancer.

Nat Rev Cancer 21, 579–591 (2021). https://doi.org/10.1038/s41568-021-00367-9Download citationAccepted: 04 May 2021Published: 29 June 2021Issue Date: September 2021DOI: https://doi.org/10.1038/s41568-021-00367-9Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard

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