Dual Mode of Regulation of Cell Division Cycle 25 A Protein by TRB3
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概要
- 論文の詳細を見る
We have recently demonstrated that TRB3, a novel stress-inducible protein, is an unstable protein regulated by the ubiquitin-proteasome system. The expression level of TRB3 protein is down-regulated by anaphase-promoting complex/cyclosome-cell division cycle division 20 homolog 1 (APC/CCdh1) through its D-box motif. Here we demonstrate that TRB3 regulates the stability of cell division cycle 25 A (Cdc25A), an essential activator of cyclin dependent kinases (CDKs). The expression level of Cdc25A protein is suppressed by over-expression of TRB3, while knockdown of TRB3 enhances the endogenous Cdc25A expression level. On the other hand, Cdc25A degradation induced by DNA damage is significantly rescued by TRB3. When serine residues in the DSG motif, which is the critical sequences for the degradation of Cdc25A induced by DNA damage, is mutated to alanine (Cdc25ADSG2X), both stimulatory and protective effects of TRB3 on the Cdc25A degradation is disappeared. TRB3 protein interacts with both wild Cdc25A and mutant Cdc25ADSG2X. Expression level of the endogenous TRB3 protein is down-regulated in a genotoxic condition. These results suggest TRB3 is a regulator for adjusting the expression level of Cdc25A both in a normal and a genotoxic conditions.
著者
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Sakai Satoshi
Department or Internal Medicine, University of Tsukuba
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Kitagawa Masatoshi
Department Of Biochemistry 1 Hamamatsu University School Of Medicine
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Hayashi Hidetoshi
Department Of Biochemistry Faculty Of Pharmaceutical Sciences Kanazawa University
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Nakanishi Makoto
Department Of Applied Chemistry Faculty Of Engineering Okayama University
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Onozaki Kikuo
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Nagoya City University
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Ohoka Nobumichi
Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City Uni
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ONOZAKI Kikuo
Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University
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Sakai Satoshi
Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University
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Sakai Satoshi
Department of Chemistry, Faculty of Science, Hokkaido University
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- Dual Mode of Regulation of Cell Division Cycle 25 A Protein by TRB3
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