An emerging model for BAP1's role in regulating cell cycle progression

Cell Biochem Biophys. 2011 Jun;60(1-2):3-11. doi: 10.1007/s12013-011-9184-6.

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.

Publication types

  • Review

MeSH terms

  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cell Line, Tumor
  • Cell Proliferation
  • E2F1 Transcription Factor / metabolism*
  • Gene Expression Regulation
  • Host Cell Factor C1 / metabolism*
  • Humans
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*

Substances

  • BAP1 protein, human
  • E2F1 Transcription Factor
  • HCFC1 protein, human
  • Host Cell Factor C1
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase