Deubiquitination of FBP1 by USP7 blocks FBP1-DNMT1 interaction and decreases the sensitivity of pancreatic cancer cells to PARP inhibitors.

ABSTRACT: Poly[ADP-ribose] polymerase (PARP) inhibitors can block DNA single-strand damage repair and subsequently increase double-stranded breaks (DSBs) by reducing the activity of the PARP1 protease and by preventing the PARP1 protein from dissociating from chromatin. Tumors with the BRCA mutation are particularly sensitive to PARP inhibitors. So far, PARP inhibitors (Olaparib) have been used to treat pancreatic cancer patients with BRCA mutation. However, these patients are prone to PARP inhibitor resistance. Our previous studies suggest that fructose-1,6-bisphosphatase 1 (FBP1) is responsible for the sensitivity to various anticancer agents, such as gemcitabine or mitogen-activated protein kinase kinase (MEK) inhibitors. In this study, we demonstrate that FBP1 regulates the sensitivity to PARP i

SUBMITTER: Cheng X 

PROVIDER: S-EPMC8978517 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature