Regulation of PTEN Phosphorylation and Stability by a Tumor Suppressor Candidate Protein
書誌事項
- 公開日
- 2004-10
- 権利情報
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- https://www.elsevier.com/tdm/userlicense/1.0/
- http://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.1074/jbc.c400377200
- 公開者
- Elsevier BV
この論文をさがす
説明
The tumor suppressor PTEN plays an essential role in regulating signaling pathways involved in cell growth and apoptosis and is inactivated in a wide variety of tumors. In this study, we have identified a protein, referred to as PICT-1 (protein interacting with carboxyl terminus 1), that binds to the C terminus of PTEN and regulates its phosphorylation and turnover. Down-regulation of PICT-1 in MCF7 cells by RNA interference enhances the degradation of PTEN with a concomitant decrease in its phosphorylation. PTEN C-terminal tumor-associated mutants, which are highly susceptible to protein degradation, have lost the ability to bind to PICT-1 along with their reduced phosphorylation, suggesting that their rapid turnover results from impaired binding to PICT-1. Our results identify PICT-1 as a PTEN-interacting protein that promotes the phosphorylation and stability of PTEN. These findings suggest a novel molecular mechanism underlying the turnover of PTEN, which also provides an explanation for the loss of PTEN function due to C-terminal mutations.
収録刊行物
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- Journal of Biological Chemistry
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Journal of Biological Chemistry 279 (44), 45300-45303, 2004-10
Elsevier BV