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, 7 (2), 137-47

Bcl-2 Expression Suppresses Mismatch Repair Activity Through Inhibition of E2F Transcriptional Activity

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Bcl-2 Expression Suppresses Mismatch Repair Activity Through Inhibition of E2F Transcriptional Activity

Cha-Kyung Youn et al. Nat Cell Biol.

Abstract

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.

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