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.