IR@PKUHSC  > 北京大学第三临床医学院  > 心血管内科
学科主题临床医学
Cables1 controls p21/Cip1 protein stability by antagonizing proteasome subunit alpha type 3
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
2015-05-07
DOI10.1038/onc.2014.171
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
WOS记录号WOS:000354190400012
Citation statistics
Cited Times:22[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62401
Collection北京大学第三临床医学院_心血管内科
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
GB/T 7714
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.
APA Shi, Z..,Li, Z..,Li, Z. J..,Cheng, K..,Du, Y..,...&Khuri, F. R..(2015).Cables1 controls p21/Cip1 protein stability by antagonizing proteasome subunit alpha type 3.ONCOGENE,34(19),2538-2545.
MLA Shi, Z.,et al."Cables1 controls p21/Cip1 protein stability by antagonizing proteasome subunit alpha type 3".ONCOGENE 34.19(2015):2538-2545.
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