Degadration of mismatch repair hMutSα heterodimer by the ubiquitin‐proteasome pathway

FEBS Letters

Lautier, Dominique²  Salles, Bernard¹  Humbert, Odile¹  Hernandez-Pigeon, Hélène²  Laurent, Guy² 

[1] Institut de Pharmacologie et Biologie Structurale, UMR 5089 CNRS, 205 route de Narbonne, 31077 Toulouse, France;INSERM U563, Centre de Physiopathologie Toulouse Purpan, Institut Claudius Regaud, 20 rue du Pont Saint-Pierre, 31052 Toulouse, France

关键词: MSH2;    MSH6;    Ubiquitination;    Protein stability;    Mismatch repair;    Proteasome;    CHX;    cycloheximide;    DCIC;    dichloroisocoumarin;    MCA;    7-amino-4-methylcoumarin;    MMR;    mismatch repair;    MSI;    microsatellite instability;    RRL;    rabbit reticulocyte lysate;    TPCK;    1-chloro-3-tosylamido-4-phenyl-2-butanone;    Ub;    ubiquitin;   

DOI  :  10.1016/S0014-5793(04)00181-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Mismatch repair plays a critical role in genome stability. This process requires several proteins including hMSH2/hMSH6 (hMutSα) heterodimer involved in the first stage of the process, the mispair recognition. We previously reported that in U937 and HL-60 cell lines, hMSH2 and hMSH6 protein expression was much lower than that in HeLa and KG1a cells. Here, we showed that the decreased expression of hMutSα results from differences in the degradation rate of both proteins by the ubiquitin-proteasome pathway. Our data suggest that in human cell lines, ubiquitin-proteasome could play an important role in the regulation of hMutSα protein expression, thereby regulating mismatch repair activity.

【 授权许可】

Unknown