Regulation of human Cdc25A stability by Serine 75 phosphorylation is not sufficient to activate a S phase checkpoint.
作者： Anastasia Goloudina , Hiroshi Yamaguchi , Daria B Chervyakova , Ettore Appella , Albert J Fornace
DOI: 10.4161/CC.2.5.482
关键词: Phosphorylation cascade 、 Cyclin-dependent kinase 、 Cell biology 、 Kinase 、 Phosphorylation 、 Biology 、 p38 mitogen-activated protein kinases 、 Signal transduction 、 CDC25A 、 CHEK1
摘要: Degradation of Cdc25A phosphatase is an ubiquitous feature stress. There are some discrepancies in the reported roles for different phosphorylation sites regulation stability. Using a panel doxycycline-inducible mutants we show that stability human protein dependent upon at S75. In non-stressed conditions and non-mitotic cells, unstable its regulated Chk1-dependent manner. During mitosis, becomes stable does not undergo degradation after DNA damage. We further Chk1 kinase regulates UV irradiation. Similar to kinase, p38 MAPK controls level osmotic phospho-specific antibodies, find both kinases can phosphorylate S75 S123 vitro. Inactivation either UV-irradiation or stress prevents activation S phase checkpoint phosphorylation. However, introduction (S75A S75/123A) proteins sufficient overcome this checkpoint. propose by may contribute only cooperation with other regulatory mechanisms.
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