CYLD: a multifunctional deubiquitinase.
The nuclear factor-kappaB (NF-kappaB) and c-Jun NH2-terminal kinase (JNK) signaling pathways regulate diverse biological processes, including the immune and inflammatory response, cell growth, apoptosis, and tumour formation. Not surprisingly therefore defects to either pathway contributes to the progression of numerous human disorders. Enhancing our understanding of the mechanisms that control signaling through these pathways is therefore significant as it may enable development of specific treatments. In this regard, CYLD was recently identified as a negative regulator of NF-kappaB and JNK signaling. CYLD has a C-terminal catalytic domain characteristic of deubiquitinating enzymes, and this is essential for CYLD to remove ubiquitin from certain proteins that positively mediate signaling through the NF-kappaB and JNK pathways. Recent studies have revealed a requirement for CYLD in many different processes and have provided some insight into the underlying mechanisms.
Glittenberg
Marcus
M
Department of Biochemistry, University of Oxford, Oxford, UK.
Ligoxygakis
Petros
P
D000818:Animals; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D000074749:Deubiquitinating Enzyme CYLD; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
D029721:Drosophila Proteins; D016328:NF-kappa B; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; D048031:JNK Mitogen-Activated Protein Kinases; D010450:Endopeptidases; C523258:CYLD protein, Drosophila; C409984:CYLD protein, human; C511601:CYLD protein, mouse; D000074749:Deubiquitinating Enzyme CYLD; D003546:Cysteine Endopeptidases