title: RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein.
abstract: The retinoblastoma susceptibility gene product, the Rb protein, is a key regulator of mammalian cell proliferation. One of the major targets of Rb is the S phase inducing E2F transcription factor. Once bound to E2F, Rb represses the expression of E2F-regulated genes. Transcriptional repression by Rb is believed to be crucial for the proper control of cell growth. Recently, we and others showed that Rb represses transcription through the recruitment of a histone deacetylase. Interestingly, we show here that the Rb-associated histone deacetylase complex could deacetylate polynucleosomal substrates, indicating that other proteins could be present within this complex. The Rb-associated protein RbAp48 belongs to many histone deacetylase complexes. We show here that the histone deacetylase HDAC1 is able to mediate the formation of a ternary complex containing Rb and RbAp48. Moreover, less deacetylase activity was found associated with Rb in cell extracts depleted for RbAp48 containing complexes, demonstrating that Rb, histone deacetylase, and RbAp48 are physically associated in live cells. Taken together, these data indicate that RbAp48 is a component of the histone deacetylase complex recruited by Rb. Finally, we found that E2F1 and RbAp48 are physically associated in the presence of Rb and HDAC1, suggesting that RbAp48 could be involved in transcriptional repression of E2F-responsive genes.
authors.affiliation: Laboratoire de Biologie Moléculaire Eucaryote, UPR 9006 CNRS, 118 route de Narbonne, 31 062 Toulouse Cedex, France.
authors.forename: E
authors.initials: E
authors.lastname: Nicolas
authors.forename: V
authors.initials: V
authors.lastname: Morales
authors.forename: L
authors.initials: L
authors.lastname: Magnaghi-Jaulin
authors.forename: A
authors.initials: A
authors.lastname: Harel-Bellan
authors.forename: H
authors.initials: H
authors.lastname: Richard-Foy
authors.forename: D
authors.initials: D
authors.lastname: Trouche
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016193:G1 Phase; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D012175:Retinoblastoma / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D056505:Retinoblastoma-Binding Protein 4; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009687:Nuclear Proteins; C082637:RBBP4 protein, human; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D056505:Retinoblastoma-Binding Protein 4; D050680:Transcription Factor DP1; D014157:Transcription Factors; D006655:Histone Deacetylases