Authors: | Pan, H.; Jia, R.; Zhang, L.; Xu, S.; Wu, Q.; Song, X.; Zhang, H.; Ge, S.; Xu, X. L.; Fan, X. |
Article Title: | BAP1 regulates cell cycle progression through E2F1 target genes and mediates transcriptional silencing via H2A monoubiquitination in uveal melanoma cells |
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. |
Keywords: | signal transduction; controlled study; unclassified drug; human cell; promoter region; protein function; protein localization; cell proliferation; cell cycle; cell cycle progression; protein protein interaction; gene expression regulation; regulatory mechanism; transcription regulation; chromatin immunoprecipitation; melanoma cell; gene silencing; uvea melanoma; tumor suppressor protein; histone h2a; cell invasion; transcription factor e2f1; e2f1; bap1; uveal melanoma; brca1 associated protein 1; histone ubiquitination; g1 phase cell cycle checkpoint; human; article; h2ak119ub1; host factor 1 |
Journal Title: | International Journal of Biochemistry and Cell Biology |
Volume: | 60 |
ISSN: | 1357-2725 |
Publisher: | Elsevier Inc. |
Date Published: | 2015-03-01 |
Start Page: | 176 |
End Page: | 184 |
Language: | English |
DOI: | 10.1016/j.biocel.2015.01.001 |
PROVIDER: | scopus |
PUBMED: | 25582751 |
DOI/URL: | |
Notes: | Export Date: 2 March 2015 -- Source: Scopus |