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学科主题: 基础医学
题名:
CREB Is a Novel Nuclear Target of PTEN Phosphatase
作者: Gu, Tingting1; Zhang, Zhong1; Wang, Jianli1; Guo, Junyi1; Shen, Wen Hong2; Yin, Yuxin1
刊名: CANCER RESEARCH
发表日期: 2011-04-15
DOI: 10.1158/0008-5472.CAN-10-3399
卷: 71, 期:8, 页:2821-2825
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: TUMOR-SUPPRESSOR PTEN ; GERMLINE MUTATIONS ; BCL-2 EXPRESSION ; COWDEN DISEASE ; PROTEIN ; TRANSCRIPTION ; GENE ; SUBUNIT
英文摘要:

PTEN phosphatase is a potent tumor suppressor that regulates multiple cellular functions. In the cytoplasm, PTEN dephosphorylates its primary lipid substrate, phosphatidylinositol 3,4,5-trisphosphate, to antagonize the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. It has also become increasingly evident that PTEN functions in the nucleus and may play an important part in transcription regulation, but its nuclear targets remain elusive. In this report, we demonstrate the transcription factor cyclic AMP response element-binding protein (CREB) is a protein target of PTEN phosphatase and that PTEN deficiency leads to CREB phosphorylation independent of the PI3K/AKT pathway. Using confocal immunofluorescence and reciprocal immunoprecipitation, we further show that PTEN colocalizes with CREB and physically interacts with CREB. Moreover, we use both in vitro and in vivo experiments to show PTEN can dephosphorylate CREB in a phosphatase-dependent manner, suggesting that CREB is a substrate of PTEN nuclear phosphatase. Loss of Pten results in an elevated RNA level of multiple CREB transcriptional targets and increased cell proliferation, which can be reversed by a nonphosphorylatable CREB mutant or knockdown of CREB. These data reveal a mechanism for PTEN modulation of CREB-mediated gene transcription and cell growth. Our study thus characterizes PTEN as a nuclear phophatase of a transcription factor and identifies CREB as a novel protein target of PTEN phosphatase, which contributes to better understanding of PTEN function in the nucleus. Cancer Res; 71(8); 2821-5. (C)2011 AACR.

语种: 英语
所属项目编号: R01 CA102447 ; 2010CB912202 ; 30930021 ; 5100003
项目资助者: NIH ; China National Major Scientific Program (973 Project) ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Shu Fan Education and Research Foundation
WOS记录号: WOS:000289507800003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64611
Appears in Collections:基础医学院_北京大学系统生物医学研究所_期刊论文

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作者单位: 1.Peking Univ, Inst Syst Biomed, Hlth Sci Ctr, Beijing 100191, Peoples R China
2.Cornell Univ, Dept Radiat Oncol, Weill Med Coll, New York, NY 10021 USA

Recommended Citation:
Gu, Tingting,Zhang, Zhong,Wang, Jianli,et al. CREB Is a Novel Nuclear Target of PTEN Phosphatase[J]. CANCER RESEARCH,2011,71(8):2821-2825.
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