Caporali Sabrina, Butera Alessio, Amelio Ivano
Chair for Systems Toxicology, Department of Biology, University of Konstanz, 78464, Constance, Germany.
Discov Oncol. 2022 Nov 1;13(1):117. doi: 10.1007/s12672-022-00579-x.
Mutations in BAP1 have been identified in a hereditary cancer predisposition syndrome and in sporadic tumours. Individuals carrying familiar BAP1 monoallelic mutations display hypersusceptibility to exposure-associated cancers, such as asbestos-driven mesothelioma, thus BAP1 status has been postulated to participate in gene-environment interaction. Intriguingly, BAP1 functions display also a high degree of tissue dependency, associated to a peculiar cancer spectrum and cell types of specific functions. Mechanistically, BAP1 functions as an ubiquitin carboxy-terminal hydrolase (UCH) and controls regulatory ubiquitination of histones as well as degradative ubiquitination of a range of protein substrates. In this article we provide an overview of the most relevant findings on BAP1, underpinning its tissue specific tumour suppressor function. We also discuss the importance of its epigenetic role versus the control of protein stability in the regulation of genomic integrity.
在一种遗传性癌症易感性综合征和散发性肿瘤中已发现BAP1的突变。携带家族性BAP1单等位基因突变的个体对暴露相关癌症表现出高度易感性，如石棉驱动的间皮瘤，因此推测BAP1状态参与基因-环境相互作用。有趣的是，BAP1的功能也表现出高度的组织依赖性，与特定的癌症谱和具有特定功能的细胞类型相关。从机制上讲，BAP1作为一种泛素羧基末端水解酶（UCH）发挥作用，控制组蛋白的调节性泛素化以及一系列蛋白质底物的降解性泛素化。在本文中，我们概述了关于BAP1的最相关研究结果，强调了其组织特异性肿瘤抑制功能。我们还讨论了其表观遗传作用与控制蛋白质稳定性在基因组完整性调节中的重要性。
