Ontology highlight
ABSTRACT:
SUBMITTER: Ahmed N
PROVIDER: S-EPMC3219826 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
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]