The COOH-terminal region of pRb2/p130 binds to histone deacetylase 1 (HDAC1), enhancing transcriptional repression of the E2F-dependent cyclin A promoter.
The tumor suppressor retinoblastoma protein family members pRb, p107, and pRb2/p130 are potent negative transcriptional regulators. The best understood target is the transcription factor E2F, which activates cell cycle-dependent transcription of genes controlling and promoting the cell division cycle (e.g., cyclin A). pRb2/p130 is known to be important in implementing cell cycle exit into G0 due to serum deprivation or various differentiation programs. Several recent studies demonstrated the effect histone acetylases and histone deacetylases (HDACs) have on fine-tuning transcriptional regulation of eucaryotic cells. In this study, we demonstrate that pRb2/p130 binds to HDAC1. This interaction increases the ability of pRb2/p130 to inhibit transcription of the E2F-dependent cyclin A promoter in vivo. We also identify the COOH-terminal 35aa as being necessary for stable interaction between HDAC1 and pRb2/p130.
Stiegler
P
P
Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
De Luca
A
A
Bagella
L
L
Giordano
A
A
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019925:Cyclin A / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D050684:E2F Transcription Factors; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019925:Cyclin A; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C489485:Rbl1 protein, mouse; C493838:Rbl2 protein, mouse; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases