FBXO22 inhibits colitis and colorectal carcinogenesis by regulating the degradation of the S2448-phosphorylated form of mTOR.

ABSTRACT: Inflammatory bowel disease (IBD) is a considerable threat to human health with a significant risk for colorectal cancer (CRC). However, currently, both the molecular pathogenesis and therapeutic treatment of IBD remain limited. In this report, using both systemic and intestinal epithelium-specific gene knockout mouse models, we demonstrate that FBXO22, a substrate receptor within the SKP1-Cullin 1-F-box family of E3 ubiquitin ligases, plays an inhibitory role in the Azoxymethane/Dextran Sodium Sulfate-induced colorectal inflammatory responses and CRC. FBXO22 targets the serine 2448-phosphorylated form of mammalian mechanistic target of rapamycin (pS2448-mTOR) for ubiquitin-dependent degradation. This proteolytic targeting effect is established based on multiple lines of evidence inc

SUBMITTER: Li M 

PROVIDER: S-EPMC11551398 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature