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PMID: 10778858 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF.

Cell ·Vol. 101 ·No. 1 ·2000-03-31 ·Pages 79-89

Zhang HS, Gavin M, Dahiya A, Postigo AA, Ma D, Luo RX, Harbour JW, Dean DC

Abstract

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.

MeSH Terms

Binding Sites CDC2-CDC28 Kinases Carrier Proteins/metabolism Cell Cycle Cell Division Cyclin A/genetics Cyclin D Cyclin E/genetics Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinases/antagonists & inhibitors,metabolism Cyclins/metabolism DNA Helicases Enzyme Inhibitors/pharmacology G1 Phase Histone Deacetylase Inhibitors Histone Deacetylases/metabolism Humans Hydroxamic Acids/pharmacology Nuclear Proteins/metabolism Phosphorylation Promoter Regions, Genetic Protein Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins Repressor Proteins/metabolism Retinoblastoma Protein/metabolism S Phase Transcription Factors/metabolism Transcription, Genetic Transfection Tumor Cells, Cultured

Chemicals

Carrier Proteins Cyclin A Cyclin D Cyclin E Cyclin-Dependent Kinase Inhibitor p16 Cyclins Enzyme Inhibitors Histone Deacetylase Inhibitors Hydroxamic Acids Nuclear Proteins Proto-Oncogene Proteins Repressor Proteins Retinoblastoma Protein SMARCA2 protein, human Transcription Factors trichostatin A Protein Serine-Threonine Kinases CDC2-CDC28 Kinases CDK2 protein, human CDK4 protein, human Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases Histone Deacetylases SMARCA4 protein, human DNA Helicases

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Zhang H S

Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Gavin M

Dahiya A

Postigo A A

Ma D

Luo R X

Harbour J W

Dean D C

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/S0092-8674(00)80625-X

Published

2000-03-31

Pages

79-89

Language

English

Region

United States

NLM ID

0413066

Subset

External Links

PubMed source DOI: 10.1016/S0092-8674(00)80625-X View journal details

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Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF.

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