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Plk3 inhibits pro‐apoptotic activity of p73 through physical interaction and phosphorylation
Author(s) -
Sang Meixiang,
Ando Kiyohiro,
Okoshi Rintaro,
Koida Nami,
Li Yuanyuan,
Zhu Yuyan,
Shimozato Osamu,
Geng Cuizhi,
Shan Baoen,
Nakagawara Akira,
Ozaki Toshinori
Publication year - 2009
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2009.01309.x
Subject(s) - biology , kinase , phosphorylation , apoptosis , polo like kinase , microbiology and biotechnology , immunoprecipitation , cell cycle , biochemistry , gene
Plk3, one of Polo‐like kinase family members, is involved in the regulation of cell cycle progression and DNA damage response. In this study, we found that Plk3 inhibits pro‐apoptotic activity of p73 through physical interaction and phosphorylation. During cisplatin (CDDP)‐mediated apoptosis, Plk3 was transcriptionally induced, whereas its protein level was kept at basal level, suggesting that Plk3 might rapidly degrade in response to CDDP. Immunoprecipitation and in vitro pull‐down experiments demonstrated that Plk3 interacts with p73. Luciferase reporter assays and RT‐PCR experiments revealed that Plk3 inhibits p73‐mediated transcriptional activity. Consistent with these results, pro‐apoptotic activity of p73 was blocked by Plk3. Additionally, Plk3 decreased the stability of p73. Intriguingly, kinase‐deficient Plk3 failed to inhibit p73 function, indicating that kinase activity of Plk3 is required for Plk3‐mediated inhibition of p73. Indeed, in vitro kinase reaction showed that NH 2 ‐terminal portion of p73 is phosphorylated by Plk3. In accordance with these observations, knocking down of Plk3 increased the stability of p73 and promoted CDDP‐mediated apoptosis in association with up‐regulation of p73. Collectively, our present findings suggest that Plk3 plays an important role in the regulation of cell fate determination in response to DNA damage through the inhibition of p73.