Szczepanski Aileen Patricia, Wang Lu
Simpson Querrey Center for Epigenetics and the Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, 303 East Superior Street, Chicago, IL, 60611, USA.
Cell Death Discov. 2021 Jan 22;7(1):20. doi: 10.1038/s41420-021-00406-2.
Histone H2AK119 mono-ubiquitination (H2AK119Ub) is a relatively abundant histone modification, mainly catalyzed by the Polycomb Repressive Complex 1 (PRC1) to regulate Polycomb-mediated transcriptional repression of downstream target genes. Consequently, H2AK119Ub can also be dynamically reversed by the BAP1 complex, an evolutionarily conserved multiprotein complex that functions as a general transcriptional activator. In previous studies, it has been reported that the BAP1 complex consists of important biological roles in development, metabolism, and cancer. However, identifying the BAP1 complex's regulatory mechanisms remains to be elucidated due to its various complex forms and its ability to target non-histone substrates. In this review, we will summarize recent findings that have contributed to the diverse functional role of the BAP1 complex and further discuss the potential in targeting BAP1 for therapeutic use.
组蛋白H2AK119单泛素化（H2AK119Ub）是一种相对丰富的组蛋白修饰，主要由多梳抑制复合物1（PRC1）催化，以调节多梳介导的下游靶基因的转录抑制。因此，H2AK119Ub也可以被BAP1复合物动态逆转，BAP1复合物是一种进化上保守的多蛋白复合物，作为一种一般的转录激活因子发挥作用。在先前的研究中，已经报道BAP1复合物在发育、代谢和癌症中具有重要的生物学作用。然而，由于其各种复杂的形式及其靶向非组蛋白底物的能力，确定BAP1复合物的调控机制仍有待阐明。在这篇综述中，我们将总结最近的研究发现，这些发现有助于揭示BAP1复合物的多种功能作用，并进一步讨论将BAP1作为治疗靶点的潜力。
