Ontology highlight
ABSTRACT:
SUBMITTER: Ahmed N
PROVIDER: S-EPMC3219826 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
Ahmed Neesar N Zeng Minghui M Sinha Indrajit I Polin Lisa L Wei Wei-Zen WZ Rathinam Chozhavendan C Flavell Richard R Massoumi Ramin R Venuprasad K K
Nature immunology 20111106 12
Chronic inflammation has been strongly associated with tumor progression, but the underlying mechanisms remain elusive. Here we demonstrate that E3 ligase Itch and deubiquitinase Cyld formed a complex via interaction through 'WW-PPXY' motifs. The Itch-Cyld complex sequentially cleaved Lys63-linked ubiquitin chains and catalyzed Lys48-linked ubiquitination on the kinase Tak1 to terminate inflammatory signaling via tumor necrosis factor. Reconstitution of wild-type Cyld but not the mutant Cyld(Y48 ...[more]