BAP1 regulates cell cycle progression through E2F1 target genes and mediates transcriptional silencing via H2A monoubiquitination in uveal melanoma cells. (March 2015)

• Record Type: Journal Article
• Authors: Pan, Hui; Jia, Renbing; Zhang, Leilei; Xu, Shiqiong; Wu, Qing; Song, Xin; Zhang, He; Ge, Shengfang; Leon Xu, Xiaoliang; Fan, Xianqun
• Is Part Of: International journal of biochemistry & cell biology. Volume 60(2015:Mar.)
• Page Start: 176
• Page End: 184
• Publication Date: 2015-03
• Subjects: ASXL1 additional sex combs-like 1 -- BAP1 BRCA1 associated protein-1 -- BRCA1 breast cancer gene 1 -- CSC cancer stem cells (CSC) -- DTB double thymidine block -- DUB deubiquitinating enzyme -- E2F1 E2F transcription factor 1 -- FOXK the forkhead transcription factor -- GNAQ G protein alpha subunit, alpha 11 -- GNA11 G protein alpha subunit, alpha 11 -- H2AK119ub1 lysine 119 monoubiquitylation on histone H2A -- h3k4 histone H3 lysine 4 -- HMT histone methyltransferases -- PR-DUB polycomb repressive-DUB -- KDM1B lysine specific demethylase 1B -- OGT O-linked N-acetylglucosaminetransferase -- SD standard deviation -- siRNA small interfering RNA -- scr scrambled -- UM uveal melanoma; BAP1 -- Uveal melanoma -- Cell cycle -- E2F1 -- H2AK119ub1; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2015.01.001
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Uveal melanoma (UM) is the most common form of primary intraocular malignancy in adult and has the tendency to metastasize. BAP1 mutations are frequently found in UM and are associated with a poor prognosis. The role of BAP1 in cell cycle regulation is currently a research highlight, but its underlying mechanism is not well understood. Here, we report that BAP1 knockdown can lead to G1 arrest and is accompanied by a decrease in the expression of S phase genes in OCM1 cells. Furthermore, in chromatin immunoprecipitation experiments, BAP1 could bind to E2F1 responsive promoters and the localization of BAP1 to E2F1-responsive promoters is host cell factor-1 dependent. Moreover, BAP1 knockdown leads to increased H2AK119ub1 levels on E2F responsive promoters. Together, these results provide new insight into the mechanisms of BAP1 in cell cycle regulation.