Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb

Cancer Cell. 2002 Nov;2(5):387-99. doi: 10.1016/s1535-6108(02)00182-4.

Abstract

DNA tumor virus oncoproteins bind and inactivate Rb by interfering with the Rb/HDAC1 interaction. Che-1 is a recently identified human Rb binding protein that inhibits the Rb growth suppressing function. Here we show that Che-1 contacts the Rb pocket region and competes with HDAC1 for Rb binding site, removing HDAC1 from the Rb/E2F complex in vitro and from the E2F target promoters in vivo. Che-1 overexpression activates DNA synthesis in quiescent NIH-3T3 cells through HDAC1 displacement. Consistently, Che-1-specific RNA interference affects E2F activity and cell proliferation in human fibroblasts but not in the pocket protein-defective 293 cells. These findings indicate the existence of a pathway of Rb regulation supporting Che-1 as the cellular counterpart of DNA tumor virus oncoproteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins*
  • Cell Division
  • Cell Line
  • Conserved Sequence
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • Glutathione / metabolism
  • Histone Deacetylase 1
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Mice
  • Models, Biological
  • Mutation
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins*
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism
  • Retinoblastoma Protein / physiology*
  • Sequence Alignment
  • Sequence Deletion
  • Transcription Factors / metabolism

Substances

  • AATF protein, human
  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Retinoblastoma Protein
  • Transcription Factors
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylases
  • Glutathione