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