Degadration of mismatch repair hMutSalpha heterodimer by the ubiquitin-proteasome pathway.
Mismatch repair plays a critical role in genome stability. This process requires several proteins including hMSH2/hMSH6 (hMutSalpha) 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 hMutSalpha 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 hMutSalpha protein expression, thereby regulating mismatch repair activity.
Hernandez-Pigeon
Hélène
H
INSERM U563, Centre de Physiopathologie Toulouse Purpan, Institut Claudius Regaud, 20 rue du Pont Saint-Pierre, 31052 Toulouse, France.
Laurent
Guy
G
Humbert
Odile
O
Salles
Bernard
B
Lautier
Dominique
D
D020137:Base Pair Mismatch; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D051718:MutS Homolog 2 Protein; D046988:Proteasome Endopeptidase Complex; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D009097:Multienzyme Complexes; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein