Skp2 regulates DNA damage repair and apoptosis via interaction with Ku70
作者： Jing Jia , Dongmei Yan , Yizhe Wang , Mengyuan Liu , Zhenyu Jia
DOI: 10.1016/J.YEXCR.2020.112335
关键词: Apoptosis 、 Cell biology 、 Binding site 、 Function (biology) 、 Ku70 、 SKP2 、 Biology 、 Gene knockdown 、 Metastasis 、 DNA damage
摘要: Abstract Purpose Skp2, an oncoprotein, regulates tumor proliferation, invasion and metastasis. Ku70 is a critical component of the non-homologous end-joining (NHEJ) process. Both Skp2 are positively associated in multiple cancers. However, there no report about relationship between proteins. Methods In this study, we carried out Bioinformatics molecular biological methods to investigate Results We first observed mRNAs were significantly increased cervical cancer tissues. And identified as Skp2-binding protein binding site located C–terminal protein. further found that knockdown decreased level cells, increase cellular apoptosis DNA damage, suggesting mediates stability function via post-translational modification. Conclusion The direct interaction proteins damage repair by regulating mechanisms how stabilize would be clarified our following research work.
sci-hub.st 参考文章(45)
Ovidiu V. Bochis, Alexandru Irimie, Martin Pichler, Ioana Berindan- Neagoe, The Role of Skp2 and its Substrate CDKN1B (p27) in Colorectal Cancer Journal of Gastrointestinal and Liver Diseases. ,vol. 24, pp. 225- 234 ,(2015) , 10.15403/JGLD.2014.1121.242.SKP2
Bo Li, Wenfu Lu, Qing Yang, Xiuping Yu, Robert J. Matusik, Zhenbang Chen, Skp2 regulates androgen receptor through ubiquitin-mediated degradation independent of Akt/mTOR pathways in prostate cancer The Prostate. ,vol. 74, pp. 421- 432 ,(2014) , 10.1002/PROS.22763
V Gama, J A Gomez, L D Mayo, M W Jackson, D Danielpour, K Song, A L Haas, M J Laughlin, S Matsuyama, Hdm2 is a ubiquitin ligase of Ku70-Akt promotes cell survival by inhibiting Hdm2-dependent Ku70 destabilization Cell Death & Differentiation. ,vol. 16, pp. 758- 769 ,(2009) , 10.1038/CDD.2009.6
Juan Wu, Xian Zhang, Ling Zhang, Ching-Yuan Wu, Abdol Hossein Rezaeian, Chia-Hsin Chan, Ju-Mei Li, Jing Wang, Yuan Gao, Fei Han, Yun Seong Jeong, Xiandao Yuan, Kum Kum Khanna, Jianping Jin, Yi-Xin Zeng, Hui-Kuan Lin, None, Skp2 E3 Ligase Integrates ATM Activation and Homologous Recombination Repair by Ubiquitinating NBS1 Molecular Cell. ,vol. 46, pp. 351- 361 ,(2012) , 10.1016/J.MOLCEL.2012.02.018
Motoshi Sawada, Weiyong Sun, Paulette Hayes, Konstantin Leskov, David A. Boothman, Shigemi Matsuyama, Ku70 suppresses the apoptotic translocation of Bax to mitochondria Nature Cell Biology. ,vol. 5, pp. 320- 329 ,(2003) , 10.1038/NCB950
C Beskow, J Skikuniene, Å Holgersson, B Nilsson, R Lewensohn, L Kanter, K Viktorsson, Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86 British Journal of Cancer. ,vol. 101, pp. 816- 821 ,(2009) , 10.1038/SJ.BJC.6605201
Daniela Hoeller, Ivan Dikic, Targeting the ubiquitin system in cancer therapy Nature. ,vol. 458, pp. 438- 444 ,(2009) , 10.1038/NATURE07960
Zhonglei Lu, Frederick Bauzon, Hao Fu, Jinhua Cui, Hongling Zhao, Keiko Nakayama, Keiich I. Nakayama, Liang Zhu, Skp2 suppresses apoptosis in Rb1-deficient tumours by limiting E2F1 activity. Nature Communications. ,vol. 5, pp. 3463- 3463 ,(2014) , 10.1038/NCOMMS4463
Sang Hyun Lee, Frank McCormick, Downregulation of Skp2 and p27/Kip1 synergistically induces apoptosis in T98G glioblastoma cells Journal of Molecular Medicine. ,vol. 83, pp. 296- 307 ,(2005) , 10.1007/S00109-004-0611-7
Chia-Hsin Chan, Chien-Feng Li, Wei-Lei Yang, Yuan Gao, Szu-Wei Lee, Zizhen Feng, Hsuan-Ying Huang, Kelvin K.C. Tsai, Leo G. Flores, Yiping Shao, John D. Hazle, Dihua Yu, Wenyi Wei, Dos Sarbassov, Mien-Chie Hung, Keiichi I. Nakayama, Hui-Kuan Lin, The Skp2-SCF E3 ligase regulates akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis Cell. ,vol. 149, pp. 1098- 1111 ,(2012) , 10.1016/J.CELL.2012.02.065