Department of Emergency, Jiangxi Provincial People's Hospital Affiliated To Nanchang University, Nanchang, 330006, Jiangxi, China.
J Mol Med (Berl). 2021 Oct;99(10):1335-1347. doi: 10.1007/s00109-021-02107-w. Epub 2021 Jul 1.
Gene transcription is strictly controlled by transcriptional complexes, which are assemblies of transcription factors, transcriptional regulators, and co-regulators. Mammalian genomes encode two C-terminal-binding proteins (CtBPs), CtBP1 and CtBP2, which are both well-known transcriptional corepressors of oncogenic processes. Their overexpression in tumors is associated with malignant behavior, such as uncontrolled cell proliferation, migration, and invasion, as well as with an increase in the epithelial-mesenchymal transition. CtBPs coordinate with other transcriptional regulators, such as histone deacetylases (HDACs) and histone acetyltransferases (p300 and CBP [CREBP-binding protein]) that contain the PXDLS motif, and with transcription factors to assemble transcriptional complexes that dock onto the promoters of genes to initiate gene transcription. Emerging evidence suggests that CtBPs function as both corepressors and coactivators in different biological processes ranging from apoptosis to inflammation and osteogenesis. Therapeutic targeting of CtBPs or the interactions required to form transcriptional complexes has also shown promising effects in preventing disease progression. This review summarizes the most recent progress in the study of CtBP functions and therapeutic inhibitors in different biological processes. This knowledge may enable a better understanding of the complexity of the roles of CtBPs, while providing new insights into therapeutic strategies that target CtBPs.
基因转录受到转录复合物的严格调控，转录复合物由转录因子、转录调节剂和共调节剂组成。哺乳动物基因组编码两个 C 端结合蛋白（CtBPs），CtBP1 和 CtBP2，它们都是致癌过程中众所周知的转录核心抑制剂。它们在肿瘤中的过度表达与恶性行为有关，如不受控制的细胞增殖、迁移和侵袭，以及上皮-间充质转化的增加。CtBPs 与其他转录调节剂（如组蛋白去乙酰化酶（HDACs）和组蛋白乙酰转移酶（p300 和 CBP[CREBP 结合蛋白]）协同作用，这些调节剂包含 PXDLS 基序，并与转录因子一起组装转录复合物，该复合物与基因的启动子结合，启动基因转录。新出现的证据表明，CtBPs 在从细胞凋亡到炎症和成骨等不同生物学过程中既作为核心抑制剂又作为共激活剂发挥作用。针对 CtBPs 或形成转录复合物所需的相互作用的治疗靶向也已显示出在预防疾病进展方面的有前景的效果。这篇综述总结了 CtBP 在不同生物学过程中的功能和治疗抑制剂的最新研究进展。这些知识可以帮助更好地理解 CtBPs 作用的复杂性，同时为针对 CtBPs 的治疗策略提供新的见解。
