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学科主题: 基础医学
题名:
PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway
作者: Ma, Xi1; Zhao, Hongshan1; Shan, Jingxuan1; Long, Feng1; Chen, Yaoyao1; Chen, Yingyu1; Zhang, Yingmei1; Han, Xiao1; Ma, Dalong1
刊名: MOLECULAR BIOLOGY OF THE CELL
发表日期: 2007-06-01
DOI: 10.1091/mbc.E06-07-0608
卷: 18, 期:6, 页:1965-1978
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: CEREBRAL CAVERNOUS MALFORMATIONS ; STE20-LIKE KINASE ; MAMMALIAN-CELLS ; CANCER CELLS ; GENE ; APOPTOSIS ; MUTATIONS ; PROTEINS ; CLONING ; SYSTEM
英文摘要:

PDCD10 (programmed cell death 10, TFAR15), a novel protein associated with cell apoptosis has been recently implicated in mutations associated with Cerebral Cavernous Malformations (CCM). Yeast two-hybrid screening revealed that PDCD10 interacts with MST4, a member of Ste20-related kinases. This interaction was confirmed by coimmunoprecipitation and colocalization assays in mammalian cells. Furthermore, the co-overexpression of PDCD10 and MST4 promoted cell proliferation and transformation via modulation of the extracellular signal-regulated kinase (ERK) pathway. Potent short interfering RNAs (siRNAs) against PDCD10 (siPDCD10) and MST4 (siMST4) were designed to specifically inhibit the expression of PDCD10 and MST4 mRNA, respectively. The induction of siPDCD10 or siMST4 resulted in decreased expression of endogenous PDCD10 or MST4, which was accompanied by reduced ERK activity and attenuated cell growth and anchorage-independent growth. On the other hand, siMST4 had similar effects in PDCD10-overexpressed cells. And more importantly, we confirmed that either overexpressing or endogenous PDCD10 can increase the MST4 kinase activity in vitro. Our results demonstrated that PDCD10 modulation of ERK signaling was mediated by MST4, and PDCD10 could be a regulatory adaptor necessary for MST4 function, suggesting a link between cerebral cavernous malformation pathogenesis and the ERK-MAPK cascade via PDCD10/MST4.

语种: 英语
WOS记录号: WOS:000246977600001
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51993
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Shanghai Genom Inc, Shanghai 201203, Peoples R China
2.Peking Univ, Sch Basic Med, Dept Immunol, Beijing 100083, Peoples R China
3.Peking Univ, Human Dis Genom Ctr, Beijing 100083, Peoples R China

Recommended Citation:
Ma, Xi,Zhao, Hongshan,Shan, Jingxuan,et al. PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway[J]. MOLECULAR BIOLOGY OF THE CELL,2007,18(6):1965-1978.
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