北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第三临床医学院  > 心血管内科  > 期刊论文
学科主题: 临床医学
题名:
Cables1 controls p21/Cip1 protein stability by antagonizing proteasome subunit alpha type 3
作者: Shi, Z.1,2,3; Li, Z.3; Li, Z. J.3,4; Cheng, K.3,5; Du, Y.3,6; Fu, H.3,6,7; Khuri, F. R.6,7
刊名: ONCOGENE
发表日期: 2015-05-07
DOI: 10.1038/onc.2014.171
卷: 34, 期:19, 页:2538-2545
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
研究领域[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
关键词[WOS]: CHROMOSOME 18Q ; MEDIATED DEGRADATION ; DEPENDENT REGULATION ; COLORECTAL-CANCER ; UBIQUITIN LIGASE ; OVARIAN-CANCER ; S-PHASE ; P21 ; GENE ; PHOSPHORYLATION
英文摘要:

The cyclin-dependent kinase (CDK) inhibitor 1A, p21/Cip1, is a vital cell cycle regulator, dysregulation of which has been associated with a large number of human malignancies. One critical mechanism that controls p21 function is through its degradation, which allows the activation of its associated cell cycle-promoting kinases, CDK2 and CDK4. Thus delineating how p21 is stabilized and degraded will enhance our understanding of cell growth control and offer a basis for potential therapeutic interventions. Here we report a novel regulatory mechanism that controls the dynamic status of p21 through its interaction with Cdk5 and Abl enzyme substrate 1 (Cables1). Cables1 has a proposed role as a tumor suppressor. We found that upregulation of Cables1 protein was correlated with increased half-life of p21 protein, which was attributed to Cables1/p21 complex formation and supported by their co-localization in the nucleus. Mechanistically, Cables1 interferes with the proteasome (Prosome, Macropain) subunit alpha type 3 (PSMA3) binding to p21 and protects p21 from PSMA3-mediated proteasomal degradation. Moreover, silencing of p21 partially reverses the ability of Cables1 to induce cell death and inhibit cell proliferation. In further support of a potential pathophysiological role of Cables1, the expression level of Cables1 is tightly associated with p21 in both cancer cell lines and human lung cancer patient tumor samples. Together, these results suggest Cables1 as a novel p21 regulator through maintaining p21 stability and support the model that the tumor-suppressive function of Cables1 occurs at least in part through enhancing the tumor-suppressive activity of p21.

语种: 英语
所属项目编号: P01 CA116676 ; 31271444 ; 81201726 ; 21612407 ; 14200010 ; 20124401120007
项目资助者: National Institutes of Health Grant ; Georgia Cancer Coalition ; Chinese National Natural Science Foundation ; Foundation for Research Cultivation and Innovation of Jinan University ; Science and Technology Program of Guangzhou ; Specialized Research Fund for the Doctoral Program of Higher Education
WOS记录号: WOS:000354190400012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62401
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Jinan Univ, Coll Life Sci & Technol, Dept Cell Biol, Guangzhou, Guangdong, Peoples R China
2.Jinan Univ, Coll Life Sci & Technol, Inst Biomed, Guangzhou, Guangdong, Peoples R China
3.Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA
4.Peking Univ, Hosp 3, Inst Vasc Med, Beijing, Peoples R China
5.Lishui Inst Agr Sci, Chem Biol Ctr, Lishui, Peoples R China
6.Emory Univ, Emory Chem Biol Discovery Ctr, Atlanta, GA 30322 USA
7.Emory Univ, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA

Recommended Citation:
Shi, Z.,Li, Z.,Li, Z. J.,et al. Cables1 controls p21/Cip1 protein stability by antagonizing proteasome subunit alpha type 3[J]. ONCOGENE,2015,34(19):2538-2545.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Shi, Z.]'s Articles
[Li, Z.]'s Articles
[Li, Z. J.]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Shi, Z.]‘s Articles
[Li, Z.]‘s Articles
[Li, Z. J.]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace