2. Academic Validation
  3. Skp2 regulates DNA damage repair and apoptosis via interaction with Ku70

Skp2 regulates DNA damage repair and apoptosis via interaction with Ku70

  • Exp Cell Res. 2020 Dec 1;397(1):112335. doi: 10.1016/j.yexcr.2020.112335.
Jing Jia 1,  Dongmei Yan 2,  Yizhe Wang 2,  Mengyuan Liu 3,  Zhenyu Jia 4,  Lei Luo 5,  Juan Ren 2,  Jianfei Fang 6,  Haining Yuan 2,  Yanyan Zhao 7,  Yongfei Song 2,  Yihui He 8,  Xiaoju Wang 9
Affiliations

Affiliations

  • 1 Center for Molecular Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, 310013, PR China. Electronic address: jiajing@zjams.com.cn.
  • 2 Center for Molecular Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, 310013, PR China.
  • 3 College of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, 310059, PR China.
  • 4 Institute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, 310013, PR China.
  • 5 College of Medicine, JiaXing University, Jiaxing, Zhejiang, 314001, PR China.
  • 6 Department of Pathology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310013, China.
  • 7 Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
  • 8 Institute of Viral Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, 310013, PR China.
  • 9 Center for Molecular Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, 310013, PR China. Electronic address: wangxj@zjams.com.cn.
PMID: 33132134 DOI: 10.1016/j.yexcr.2020.112335
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 and Ku70 are positively associated in multiple cancers. However, there is no report about the relationship between Skp2 and Ku70 proteins.

Methods: In this study, we carried out Bioinformatics and molecular biological methods to investigate the relationship between Skp2 and Ku70 proteins.

Results: We first observed Skp2 and Ku70 mRNAs were significantly increased in cervical Cancer tissues. And we identified Ku70 as a Skp2-binding protein and the binding site located in the C-terminal of Ku70 protein. We further found that Skp2 knockdown decreased the Ku70 protein level in cells, and increase the cellular Apoptosis and DNA damage, suggesting Skp2 mediates the Ku70 protein stability and function via post-translational modification.

Conclusion: The direct interaction between Skp2 and Ku70 proteins mediates the DNA damage repair and cellular Apoptosis by regulating Ku70 stability and function via post-translational modification. The molecular mechanisms how Skp2 stabilize Ku70 would be clarified in our following research work.

Keywords

Cervical cancer; Ku70; Post-translational modification; Protein interaction; S-phase kinase–associated protein2.

Figures
Products