USP39 regulates DNA damage response and chemo-radiation resistance by deubiquitinating and stabilizing CHK2

Jinhuan Wu, Yuping Chen, Guohe Geng, Lei Li, Ping Yin, Somaira Nowsheen, Yunhui Li, Chenming Wu, Jiaqi Liu, Fei Zhao, Wootae Kim, Qin Zhou, Jinzhou Huang, Guijie Guo, Chao Zhang, Xinyi Tu, Xiumei Gao, Zhenkun Lou, Kuntian Luo, Haixuan Qiao & 1 others Jian Yuan

Research output: Contribution to journalArticle

Abstract

The serine/threonine kinase, CHK2 (checkpoint kinase 2), is a key mediator in DNA damage response and a tumor suppressor, which is implicated in promoting cell cycle arrest, apoptosis and DNA repair. Accumulating evidence suggests that these functions are primarily exerted through phosphorylation downstream factors such as p53 and BRCA1. Recent studies have shown that ubiquitination is an important mode of regulation of CHK2. However, it remains largely unclear whether deubiquitinases participate in regulation of CHK2. Here, we report that a deubiquitinase, USP39, is a new regulator of CHK2. Mechanistically, USP39 deubiquitinates and stabilizes CHK2, which in turn enhances CHK2 stability. Short hairpin RNA (shRNA) mediated knockdown of USP39 led to deregulate CHK2, which resulted in compromising the DNA damage-induced G2/M checkpoint, decreasing apoptosis, and conferring cancer cells resistance to chemotherapy drugs and radiation treatment. Collectively, we identify USP39 as a novel regulator of CHK2 in the DNA damage response.

Original languageEnglish (US)
Pages (from-to)114-124
Number of pages11
JournalCancer Letters
Volume449
DOIs
StatePublished - May 1 2019

Fingerprint

Checkpoint Kinase 2
DNA Damage
Radiation
Apoptosis
Protein-Serine-Threonine Kinases
Ubiquitination
Cell Cycle Checkpoints
DNA Repair
Small Interfering RNA
Neoplasms
Phosphorylation

Keywords

  • Chemo-radiation resistance
  • CHK2
  • Deubiquitination
  • Lung cancer
  • USP39

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

USP39 regulates DNA damage response and chemo-radiation resistance by deubiquitinating and stabilizing CHK2. / Wu, Jinhuan; Chen, Yuping; Geng, Guohe; Li, Lei; Yin, Ping; Nowsheen, Somaira; Li, Yunhui; Wu, Chenming; Liu, Jiaqi; Zhao, Fei; Kim, Wootae; Zhou, Qin; Huang, Jinzhou; Guo, Guijie; Zhang, Chao; Tu, Xinyi; Gao, Xiumei; Lou, Zhenkun; Luo, Kuntian; Qiao, Haixuan; Yuan, Jian.

In: Cancer Letters, Vol. 449, 01.05.2019, p. 114-124.

Research output: Contribution to journalArticle

Wu, J, Chen, Y, Geng, G, Li, L, Yin, P, Nowsheen, S, Li, Y, Wu, C, Liu, J, Zhao, F, Kim, W, Zhou, Q, Huang, J, Guo, G, Zhang, C, Tu, X, Gao, X, Lou, Z, Luo, K, Qiao, H & Yuan, J 2019, 'USP39 regulates DNA damage response and chemo-radiation resistance by deubiquitinating and stabilizing CHK2', Cancer Letters, vol. 449, pp. 114-124. https://doi.org/10.1016/j.canlet.2019.02.015
Wu, Jinhuan ; Chen, Yuping ; Geng, Guohe ; Li, Lei ; Yin, Ping ; Nowsheen, Somaira ; Li, Yunhui ; Wu, Chenming ; Liu, Jiaqi ; Zhao, Fei ; Kim, Wootae ; Zhou, Qin ; Huang, Jinzhou ; Guo, Guijie ; Zhang, Chao ; Tu, Xinyi ; Gao, Xiumei ; Lou, Zhenkun ; Luo, Kuntian ; Qiao, Haixuan ; Yuan, Jian. / USP39 regulates DNA damage response and chemo-radiation resistance by deubiquitinating and stabilizing CHK2. In: Cancer Letters. 2019 ; Vol. 449. pp. 114-124.
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AU - Wu, Jinhuan

AU - Chen, Yuping

AU - Geng, Guohe

AU - Li, Lei

AU - Yin, Ping

AU - Nowsheen, Somaira

AU - Li, Yunhui

AU - Wu, Chenming

AU - Liu, Jiaqi

AU - Zhao, Fei

AU - Kim, Wootae

AU - Zhou, Qin

AU - Huang, Jinzhou

AU - Guo, Guijie

AU - Zhang, Chao

AU - Tu, Xinyi

AU - Gao, Xiumei

AU - Lou, Zhenkun

AU - Luo, Kuntian

AU - Qiao, Haixuan

AU - Yuan, Jian

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