Cantor David J, David Gregory
a Department of Biochemistry and Molecular Pharmacology , New York University School of Medicine , New York , NY , USA.
b Department of Urology.
Expert Opin Ther Targets. 2017 Nov;21(11):1051-1061. doi: 10.1080/14728222.2017.1386655. Epub 2017 Oct 9.
Sin3B serves as a scaffold for chromatin-modifying complexes that repress gene transcription to regulate distinct biological processes. Sin3B-containing complexes are critical for cell cycle withdrawal, and abrogation of Sin3B-dependent cell cycle exit impacts tumor progression. Areas covered: In this review, we discuss the biochemical characteristics of Sin3B-containing complexes and explore how these complexes regulate gene transcription. We focus on how Sin3B-containing complexes, through the association of the Rb family of proteins, repress the expression of E2F target genes during quiescence, differentiation, and senescence. Finally, we speculate on the potential benefits of the inhibition of Sin3B-containing complexes for the treatment of cancer. Expert opinion: Further identification and characterization of specific Sin3B-containing complexes provide a unique opportunity to prevent the pro-tumorigenic effects of the senescence-associated secretory phenotype, and to abrogate cancer stem cell quiescence and the associated resistance to therapy.
Sin3B作为染色质修饰复合物的支架，可抑制基因转录以调节不同的生物学过程。含Sin3B的复合物对细胞周期退出至关重要，而消除Sin3B依赖性细胞周期退出会影响肿瘤进展。涵盖领域：在本综述中，我们讨论了含Sin3B复合物的生化特性，并探讨了这些复合物如何调节基因转录。我们重点关注含Sin3B的复合物如何通过与Rb蛋白家族的关联，在静止、分化和衰老过程中抑制E2F靶基因的表达。最后，我们推测抑制含Sin3B复合物对癌症治疗的潜在益处。专家观点：进一步鉴定和表征特定的含Sin3B复合物，为预防衰老相关分泌表型的促肿瘤作用、消除癌症干细胞静止状态及相关的治疗抗性提供了独特的机会。
