Interaction of mismatch repair protein PMS2 and the p53-related transcription factor p73 in apoptosis response to cisplatin.
Mismatch repair (MMR) proteins contribute to genome integrity by correcting replication errors. In higher eukaryotes, MMR proteins also regulate the cellular response to DNA lesions such as oxidized, alkylated, or crosslinked bases. Previous studies have linked MMR proteins to the activation of apoptosis through p53-dependent and p53-independent mechanisms. MMR-deficient cells exhibit variable defects in the induction of p53 and its related p73, which are activators of apoptosis. However, the specific role of each MMR protein in the regulation of apoptosis has not been determined. Here, we describe an interaction between PMS2, an MMR protein, and p73. This interaction causes the stabilization of p73 and the redistribution of PMS2 to the nuclear compartment. Exposure to cisplatin enhances the association between PMS2 and p73. Moreover, stimulation of the p73 proapoptotic function by cisplatin requires PMS2. These results suggest that PMS2 contributes to genome integrity not only through DNA repair but also by enhancing DNA damage-induced apoptosis.
Shimodaira
Hideki
H
Ludwig Institute for Cancer Research, University of California at San Diego, Bonner Hall 3326, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Yoshioka-Yamashita
Atsuko
A
Kolodner
Richard D
RD
Wang
Jean Y J
JY
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000494:pharmacology; D019556:COS Cells; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D015151:Immunoblotting; D008164:Luminescent Proteins / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D000070976:Mismatch Repair Endonuclease PMS2; D009369:Neoplasms / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C054562:yellow fluorescent protein, Bacteria; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes; D002945:Cisplatin