The steady-state level of CDK4 protein is regulated by antagonistic actions between PAQR4 and SKP2 and involved in tumorigenesis
文献类型：期刊论文
| 作者 | Wang, Lin1; Wei, Siying1; Cao, Qianqian1; Wang, Zhenzhen1; Chen, Yan1,4; Zhang, Rui3; You, Xue4; Zhang, Huanhuan4; Cheng, Tingting2; , |
| 刊名 | JOURNAL OF MOLECULAR CELL BIOLOGY
 |
| 出版日期 | 2017 |
| 卷号 | 9期号:5页码:409-421 |
| 关键词 | CDK4 PAQR4 SKP2 ubiquitination protein degradation tumorigenesis |
| ISSN号 | 1674-2788 |
| DOI | 10.1093/jmcb/mjx028 |
| 文献子类 | Article |
| 英文摘要 | CDK4 is crucial for G1-to-S transition of cell cycle. It is well established that ubiquitin-mediated degradations of CDK inhibitors and cyclins are pivotal for the timely and unidirectional progression of cell cycle. However, how CDK4 itself is modulated by ubiquitin-mediated degradation has been elusive. Here we report that the steady-state level of CDK4 is controlled by PAQR4, a member of the progestin and adipoQ receptor family, and SKP2, an E3 ubiquitin ligase. Knockdown of PAQR4 leads to reduction of cell proliferation, accompanied by reduced protein level of CDK4. PAQR4 reduces polyubiquitination and degradation of CDK4. PAQR4 interacts with the C-terminal lobe of CDK4. On the other hand, SKP2 also interacts with the C-terminal lobe of CDK4 and enhances polyubiquitination and degradation of CDK4. Importantly, PAQR4 and SKP2 bind to the same region in CDK4, and PAQR4 competes with SKP2 for the binding, thereby abrogating SKP2-mediated ubiquitination of CDK4. Using a two-stage DMBA/TPA-induced skin cancer model, we find that PAQR4-deleted mice are resistant to chemical carcinogen-induced tumor formation. Collectively, our findings reveal that the steady-state level of CDK4 is controlled by the antagonistic actions between PAQR4 and SKP2, contributing to modulation of cell proliferation and tumorigenesis. |
| 学科主题 | Cell Biology |
| WOS关键词 | PHOSPHORYLATION-DEPENDENT UBIQUITINATION ; CELL-CYCLE CONTROL ; F-BOX PROTEINS ; GOLGI-APPARATUS ; S PHASE ; DEGRADATION ; COMPLEX ; LIGASE ; CANCER ; SENESCENCE |
| 语种 | 英语 |
| WOS记录号 | WOS:000417761200007 |
| 出版者 | OXFORD UNIV PRESS |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1301]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Key Lab Nutr & Metab, Inst Nutr Sci,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; 2.Tongji Univ, Dept Clin Med, Shanghai 200092, Peoples R China, 3.Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Tianjin Key Lab Canc Immunol & Biotherapy, Canc Mol Diagnost Core Lab, Tianjin 300060, Peoples R China; 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Lin,Wei, Siying,Cao, Qianqian,et al. The steady-state level of CDK4 protein is regulated by antagonistic actions between PAQR4 and SKP2 and involved in tumorigenesis[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2017,9(5):409-421. |
| APA | Wang, Lin.,Wei, Siying.,Cao, Qianqian.,Wang, Zhenzhen.,Chen, Yan.,...&,.(2017).The steady-state level of CDK4 protein is regulated by antagonistic actions between PAQR4 and SKP2 and involved in tumorigenesis.JOURNAL OF MOLECULAR CELL BIOLOGY,9(5),409-421. |
| MLA | Wang, Lin,et al."The steady-state level of CDK4 protein is regulated by antagonistic actions between PAQR4 and SKP2 and involved in tumorigenesis".JOURNAL OF MOLECULAR CELL BIOLOGY 9.5(2017):409-421. |
入库方式： OAI收割
来源：上海营养与健康研究所
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