title: An emerging model for BAP1's role in regulating cell cycle progression.
abstract: BRCA1-associated protein-1 (BAP1) is a 729 residue, nuclear-localized deubiquitinating enzyme (DUB) that displays tumor suppressor properties in the BAP1-null NCI-H226 lung carcinoma cell line. Studies that have altered BAP1 cellular levels or enzymatic activity have reported defects in cell cycle progression, notably at the G1/S transition. Recently BAP1 was shown to associate with the transcriptional regulator host cell factor 1 (HCF-1). The BAP1/HCF-1 interaction is mediated by the HCF-1 Kelch domain and an HCF-1 binding motif (HBM) within BAP1. HCF-1 is modified with ubiquitin in vivo, and ectopic studies suggest BAP1 deubiquitinates HCF-1. HCF-1 is a chromatin-associated protein thought to both activate and repress transcription by linking appropriate histone-modifying enzymes to a subset of transcription factors. One known role of HCF-1 is to promote cell cycle progression at the G1/S boundary by recruiting H3K4 histone methyltransferases to the E2F1 transcription factor so that genes required for S-phase can be transcribed. Given the robust associations between BAP1/HCF-1 and HCF-1/E2Fs, it is reasonable to speculate that BAP1 influences cell proliferation at G1/S by co-regulating transcription from HCF-1/E2F-governed promoters.
authors.affiliation: Department of Biochemistry, Emory University, Atlanta, GA 30322, USA.
authors.forename: Ziad M
authors.initials: ZM
authors.lastname: Eletr
authors.forename: Keith D
authors.initials: KD
authors.lastname: Wilkinson
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D051863:Host Cell Factor C1 / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: C400134:BAP1 protein, human; D050687:E2F1 Transcription Factor; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase