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. 2000 Mar 31;101(1):79-89. doi: 10.1016/S0092-8674(00)80625-X.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

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
  • Cyclin-Dependent Kinases / 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

Substances

  • 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