Phosphorylation of the E3 ubiquitin protein ligase ITCH diminishes binding to its cognate E2 ubiquitin ligase.

ABSTRACT: Heightened and extended inflammation underlies the pathogenesis of many disorders, including inflammatory bowel disease, sepsis, and inflammatory arthritis. Ubiquitin networks help dictate the strength and duration of inflammatory signaling. In innate immunity, the itchy E3 ubiquitin protein ligase (ITCH)-A20 ubiquitin-editing complex inhibits receptor-interacting Ser/Thr kinase (RIPK) activation by removing Lys-63-linked polyubiquitinated chains from key proteins in the nuclear factor kappa B (NF-κB) signaling pathway. The complex then attaches polyubiquitinated chains to these proteins to target them for lysosomal or proteasomal destruction. ITCH is phosphorylated and thereby inhibited by inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ) to fine-tune the inflammatory respons

SUBMITTER: Perez JM 

PROVIDER: S-EPMC5777250 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature