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| Subject Categories: Signal Transduction |
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| The EMBO Journal
(2007) 26, 3062–3074, doi:10.1038/sj.emboj.7601749 Published online 14 June 2007 |
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| Phosphorylation of Pirh2 by Calmodulin-dependent kinase II impairs its ability to ubiquitinate p53 |
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| Shanshan Duan1, 4, Zhan Yao1, 4, Dezhi Hou1, Zhengsheng Wu3, Wei-guo Zhu2 and Mian Wu1 |
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1 Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China 2 Department of Biochemistry and Molecular Biology and the Cancer Research Center, Peking University Health Science Center, Beijing, China 3 Department of pathology, Anhui Medical University, Hefei, Anhui, People's Republic of China To whom correspondence should be addressed Mian Wu, School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui 230027, People's Republic of China. Tel.: +86 551 3607324; Fax: +86 551 3606264; E-mail: wumian@ustc.edu.cn 4 These authors contributed equally to this work Received 17 November 2006; Accepted 15 May 2007; Published online 14 June 2007. |
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| Abstract |
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| Although the recently identified Pirh2 protein is known as a p53-induced ubiquitin-protein E3 ligase, which negatively regulates p53, the detailed mechanism underlying the regulation of Pirh2 remains largely unknown. Here, we demonstrate that while Pirh2 is mostly detected in the phosphorylated form in normal tissues, it is predominantly present in the unphosphorylated form in majority of tumor cell lines and tissues examined. Phosphorylated Pirh2 is far more unstable than its unphosphorylated form. We further identified that Calmodulin-dependent kinase II (CaMK II) phosphorylates Pirh2 on residues Thr-154 and Ser-155. Phosphorylation of Pirh2 appears to be regulated through cell cycle-dependent mechanism. CaMK II-mediated Pirh2 phosphorylation abrogates its E3 ligase activity toward p53. Together, our data suggest that phosphorylation of Pirh2 may act as a fine-tuning to maintain the balance of p53-Pirh2 autoregulatory feedback loop, which facilitates the tight regulation of p53 stability and tumor suppression. |
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| Keywords: CaMK II, p53, phosphorylation, Pirh2, ubiquitination |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHPhosphorylation of Pirh2 by Calmodulin-dependent kinase II impairs its ability to ubiquitinate p53 The EMBO Journal Article Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR Nature Cell Biology Article (01 Jul 2008) Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase ?Synoviolin? The EMBO Journal Article Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase ?Synoviolin? The EMBO Journal Article (10 Jan 2007) |
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