Article abstract
Nature Cell Biology 7, 137 - 147 (2004)
Published online: 26 December 2004 | doi:10.1038/ncb1215
Bcl-2 expression suppresses mismatch repair activity through inhibition of E2F transcriptional activity
Cha-Kyung Youn1,2, Hyun-Ju Cho1,2, Soo-Hyun Kim1,2, Hong-Beum Kim1,2, Mi-Hwa Kim1,2, In-Youb Chang2, Jung-Sup Lee2, Myung-Hee Chung3, Kyung-Soo Hahm2 & Ho Jin You1,2
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.
- Department of Pharmacology, School of medicine, Chosun University, 375 Seusuk-dong, Gwangju 501-759, South Korea.
- Research Center for Proteinous Materials, Chosun University, 375 Seusuk-Dong, Gwangju 501-759 South Korea.
- Department of Pharmacology, School of medicine, Seoul National University, 28 Yongon-Dong, Seoul 110-799, South Korea.
Correspondence to: Ho Jin You1,2 e-mail: hjyou@chosun.ac.kr
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