Bcl-2 expression suppresses mismatch repair activity through inhibition of E2F transcriptional activity

Nat Cell Biol. 2005 Feb;7(2):137-47. doi: 10.1038/ncb1215. Epub 2004 Dec 26.


Bcl-2 stimulates mutagenesis after the exposure of cells to DNA-damaging agents. However, the biological mechanisms of Bcl-2-mediated mutagenesis have remained largely obscure. Here we demonstrate that the Bcl-2-mediated suppression of hMSH2 expression results in a reduced cellular capacity to repair mismatches. The pathway linking Bcl-2 expression to the suppression of mismatch repair (MMR) activity involves the hypophosphorylation of pRb, and then the enhancement of the E2F-pRb complex. This is followed by a decrease in hMSH2 expression. MMR has a key role in protection against deleterious mutation accumulation and in maintaining genomic stability. Therefore, the decreased MMR activity by Bcl-2 may be an underlying mechanism for Bcl-2-promoted oncogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pair Mismatch
  • CDC2-CDC28 Kinases / metabolism
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Cyclin-Dependent Kinase 2
  • DNA Repair*
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • E2F Transcription Factors
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MutS Homolog 2 Protein
  • Mutagenesis
  • Mutation
  • Neoplasms / genetics
  • Phosphorylation
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Retinoblastoma Protein / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Retinoblastoma Protein
  • Transcription Factors
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • MSH2 protein, human
  • MutS Homolog 2 Protein