BAP1 Represses Sequential Activation of IRAKs and NF-κB Signaling in Pancreatic Cancer.

ABSTRACT: The deubiquitinating enzyme BRCA1 Associated Protein-1 (BAP1) has been reported to be shallowly deleted in a subset of pancreatic ductal adenocarcinomas (PDAC) and is believed to play a significant role in the development of chronic pancreatitis-driven PDAC. However, evidence suggests that BAP1 may also be involved in the progression and metastasis of PDAC, though the underlying mechanism remains unclear. Here, we demonstrate that BAP1 deletion leads to the overactivation of the nuclear factor-κB (NF-κB) signaling in PDAC, thereby promoting the proliferation, migration, and invasion of PDAC models both in vivo and in vitro. Mechanistically, BAP1 inhibits the sequential activation of interleukin-1 receptor-associated kinases (IRAKs) in an enzyme-independent manner. BAP1 binds

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC11900812 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature