3F-Box protein 32 degrades ataxia telangiectasia and Rad3-related and regulates DNA damage response induced by gemcitabine in pancreatic cancer

Chong Yang; Ping Fan; Shikai Zhu; Hongji Yang; Xin Jin; Heshui Wu

doi:10.3892/ol.2018.8367

3F-Box protein 32 degrades ataxia telangiectasia and Rad3-related and regulates DNA damage response induced by gemcitabine in pancreatic cancer

Oncol Lett. 2018 Jun;15(6):8878-8884. doi: 10.3892/ol.2018.8367. Epub 2018 Mar 28.

Authors

Chong Yang¹, Ping Fan², Shikai Zhu¹, Hongji Yang¹, Xin Jin³, Heshui Wu³

Affiliations

¹ Organ Transplantation Center, Hospital of The University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
² Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
³ Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Abstract

Ataxia telangiectasia and Rad3-related (ATR) activates checkpoint kinase 1 (CHK1) following replication fork stalling, leading to cell cycle arrest. ATR-CHK1 pathway components are considered to be promising therapeutic targets to enhance the effectiveness of replication inhibitors. The present study revealed that F-Box protein 32 (FBXO32) regulated ATR expression in pancreatic cancer PANC-1 and MIA PaCa-2 cells. Additionally, FBXO32 interacts with ATR in PANC-1 cells and ATR is a degradation substrate of E3 ubiquitin ligase FBXO32. Furthermore, FBXO32 regulated the DNA damage response induced by gemcitabine in PANC-1 cells. Taken together, the results of the present study suggested that FBXO32, as an E3 ubiquitin ligase of ATR, regulates the DNA damage response induced by gemcitabine in pancreatic cancer.

Keywords: DNA damage; F-Box protein 32; ataxia telangiectasia and Rad3-related; degradation; gemcitabine; pancreatic cancer; ubiquitination.