Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb.
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.
Bruno
Tiziana
T
Laboratory B, Via delle Messi d'Oro 156, 00158 Rome, Italy.
De Angelis
Roberta
R
De Nicola
Francesca
F
Barbato
Christian
C
Di Padova
Monica
M
Corbi
Nicoletta
N
Libri
Valentina
V
Benassi
Barbara
B
Mattei
Elisabetta
E
Chersi
Alberto
A
Soddu
Silvia
S
Floridi
Aristide
A
Passananti
Claudio
C
Fanciulli
Maurizio
M
D016475:3T3 Cells; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005978:Glutathione / Q000378:metabolism; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016415:Sequence Alignment; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism
C402637:AATF protein, human; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D005978:Glutathione