MYC protein interactors in gene transcription and cancer

被引:213
作者
Lourenco, Corey [1 ]
Resetca, Diana [1 ,2 ]
Redel, Cornelia [1 ,2 ]
Lin, Peter [1 ,2 ]
MacDonald, Alannah S. [1 ,2 ]
Ciaccio, Roberto [3 ]
Kenney, Tristan M. G. [1 ,2 ]
Wei, Yong [1 ,4 ]
Andrews, David W. [2 ,4 ]
Sunnerhagen, Maria [5 ]
Arrowsmith, Cheryl H. [1 ,2 ,6 ]
Raught, Brian [1 ,2 ]
Penn, Linda Z. [1 ,2 ]
机构
[1] Princess Margaret Canc Ctr, Toronto, ON, Canada
[2] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada
[3] Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy
[4] Sunnybrook Res Inst, Biol Sci, Toronto, ON, Canada
[5] Linkoping Univ, Dept Phys Chem & Biol, Linkoping, Sweden
[6] Struct Genom Consortium, Toronto, ON, Canada
关键词
HISTONE ACETYLTRANSFERASE COMPLEX; TATA-BINDING PROTEIN; RNA CAP METHYLATION; RECRUITS P-TEFB; C-MYC; TRANSACTIVATION DOMAIN; IN-VIVO; SELECTIVE-INHIBITION; ESSENTIAL COFACTOR; TERMINAL DOMAIN;
D O I
10.1038/s41568-021-00367-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The 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. This Perspective highlights the importance of protein-protein interactions for the oncogenic functions of MYC and discusses how the MYC protein interactome might be exploited therapeutically.
引用
收藏
页码:579 / 591
页数:13
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