CHUK, IKBKB phosphorylate CYLD at S418

Stable Identifier
Reaction [transition]
Homo sapiens
CYLD is phosphorylated by IKK
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CYLD is a deubiquitinating enzyme (DUB) that removes K63-linked ubiquitin chains from a large number of key signaling molecules, including tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and RIPK1. CYLD knockdown in human embryonic kidney 293 cells and human cervical carcinoma HeLa cells resulted in constitutive ubiquitination of TRAF2 (Reiley W et al. 2005) At the same time stimuli-induced TRAF2 ubiquitination was associated with site-specific phosphorylation of CYLD, a molecular event that was shown to inhibit CYLD-mediated deubquitination of TRAF2 (Reiley W et al. 2005; Hutti JE et al. 2009). Phosphorylation of CYLD was detected in TNF-alpha-stimulated HEK293T and HeLa cells, in LPS-treated BJAB cells, a human B‑cell line, and in human Jurkat T cells after stimulation with mitogens (Reiley W et al. 2005). Phoshorylation of CYLD was found to depend on IKKgamma (IKBKG), since it was blocked in IKBKG-deficient Jurkat T cells (Reiley W et al. 2005). Transfection and in vitro kinase assays reveal that both IKKalpha (CHUK) and IKKbeta (IKBKB) are able to phosphorylate CYLD (Reiley W et al. 2005). The noncanonical IKK family member IKKepsilon (IKBKE) was also reported to phosphorylate CYLD at serine 418 inhibiting CYLD deubiquitinase activity. The phosphorylation of CYLD by IKKepsilon is thought to contribute to IKKepsilon-driven cell transformation (Hutti JE et al. 2009).

Literature References
PubMed ID Title Journal Year
15870263 Regulation of the deubiquitinating enzyme CYLD by IkappaB kinase gamma-dependent phosphorylation

Wu, X, Sun, SC, Reiley, W, Zhang, M, Granger, E

Mol. Cell. Biol. 2005
Catalyst Activity

protein serine/threonine kinase activity of IKBKG:p-S176,S180-CHUK:p-S177,S181-IKBKB [cytosol]

Orthologous Events
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