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学科主题: 临床医学
题名:
Cables1 Complex Couples Survival Signaling to the Cell Death Machinery
作者: Shi, Zhi1,2,3; Park, Hae R.3,4; Du, Yuhong3,5; Li, Zijian3,6; Cheng, Kejun3,7; Sun, Shi-Yong8,9; Li, Zenggang3; Fu, Haian3,5,8,9; Khuri, Fadlo R.5,8,9
刊名: CANCER RESEARCH
发表日期: 2015
DOI: 10.1158/0008-5472.CAN-14-0036
卷: 75, 期:1, 页:147-158
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]: CYCLE PROGRESSION ; 14-3-3 PROTEINS ; CHROMOSOME 18Q ; MEDIATED PHOSPHORYLATION ; CYTOPLASMIC LOCALIZATION ; REGULATING KINASE-1 ; CANCER PROGRESSION ; OVARIAN-CANCER ; LUNG-CANCER ; IN-VIVO
英文摘要:

Cables1 is a candidate tumor suppressor that negatively regulates cell growth by inhibiting cyclin-dependent kinases. Cables1 expression is lost frequently in human cancer but little is known about its regulation. Here, we report that Cables1 levels are controlled by a phosphorylation and 14-3-3-dependent mechanism. Mutagenic analyses identified two residues, T44 and T150, that are specifically critical for 14-3-3 binding and that serve as substrates for phosphorylation by the cell survival kinase Akt, which by binding directly to Cables1 recruits 14-3-3 to the complex. In cells, Cables1 overexpression induced apoptosis and inhibited cell growth in part by stabilizing p21 and decreasing Cdk2 kinase activity. Ectopic expression of activated Akt (AKT1) prevented Cables1-induced apoptosis. Clinically, levels of phosphorylated Cables1 and phosphorylated Akt correlated with each other in human lung cancer specimens, consistent with pathophysiologic significance. Together, our results illuminated a dynamic regulatory system through which activated Akt and 14-3-3 work directly together to neutralize a potent tumor suppressor function of Cables1. (C) 2014 AACR.

语种: 英语
所属项目编号: P01 CA116676 ; 31271444 ; 81201726 ; 21612407 ; 2014J4100009 ; 20124401120007
项目资助者: NIH ; Georgia Cancer Coalition ; Winship Cancer Institute Kennedy Seed grant ; Chinese National Natural Science Foundation ; Foundation for Research Cultivation and Innovation of Jinan University ; Science and Technology Program of Guangzhou ; Guangdong Natural Science Funds for Distinguished Young Scholar ; Specialized Research Fund for the Doctoral Program of Higher Education
WOS记录号: WOS:000347383000016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66448
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA
2.Emory Univ, Emory Chem Biol Discovery Ctr, Atlanta, GA 30322 USA
3.Jinan Univ, Coll Life Sci & Technol, Dept Cell Biol, Guangzhou, Guangdong, Peoples R China
4.Jinan Univ, Coll Life Sci & Technol, Inst Biomed, Guangzhou, Guangdong, Peoples R China
5.Pusan Natl Univ, Sch Dent, Dept Oral Pathol, Pusan 609735, South Korea
6.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100871, Peoples R China
7.Chem Biol Ctr, Lishui Inst Agr Sci, Lishui, Peoples R China
8.Emory Univ, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA
9.Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

Recommended Citation:
Shi, Zhi,Park, Hae R.,Du, Yuhong,et al. Cables1 Complex Couples Survival Signaling to the Cell Death Machinery[J]. CANCER RESEARCH,2015,75(1):147-158.
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