Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF.
We present evidence that Rb forms a repressor containing histone deacetylase (HDAC) and the hSWI/SNF nucleosome remodeling complex, which inhibits transcription of genes for cyclins E and A and arrests cells in the G1 phase of the cell cycle. Phosphorylation of Rb by cyclin D/cdk4 disrupts association with HDAC, relieving repression of the cyclin E gene and G1 arrest. However, the Rb-hSWI/SNF complex persists and is sufficient to maintain repression of the cyclin A and cdc2 genes, inhibiting exit from S phase. HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF then appear to maintain the order of cyclin E and A expression during the cell cycle, which in turn regulates exit from G1 and from S phase, respectively.
Zhang
H S
HS
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Gavin
M
M
Dahiya
A
A
Postigo
A A
AA
Ma
D
D
Luo
R X
RX
Harbour
J W
JW
Dean
D C
DC
D001665:Binding Sites; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D019925:Cyclin A / Q000235:genetics; D056741:Cyclin D; D019927:Cyclin E / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004265:DNA Helicases; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016193:G1 Phase; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016196:S Phase; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D019925:Cyclin A; D056741:Cyclin D; D019927:Cyclin E; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; C084011:SMARCA2 protein, human; D014157:Transcription Factors; C012589:trichostatin A; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D006655:Histone Deacetylases; C084108:SMARCA4 protein, human; D004265:DNA Helicases