Conserved helix-loop-helix ubiquitous kinase
The CHUK gene at 10q24 has 21 exones and encodes a 745 amino acid peptide that is processed to form the alpha subunit of iκß kinase (IKKα, also known as conserved helix-loop-helix ubiquitous kinase). This is activated when phosphorylated. It has an essential role in the proliferation and differentiation of the epidermis. Non functional mutations of CHUK cause the lethal cocoon syndrome. It is also mutated in some skin cancers.
It is a component of IKK which shuttles between the cytoplasm and the nucleus as part of the conventional pathway of NF-kappa-B activation and phosphorylation of inhibitors of NF-kappa-B. This leads to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. It also phosphorylates NCOA3 and Ser-10 of histone H3 at NF-kappa-B-regulated promoters found during inflammatory responses triggered by cytokines.
The bacterial toxin YopJ (the outer protein found in Yersinia pestis and Yersinia pseudotuberculosis, coded by the virulence plasmid pCD1) works by acetylation of Thr-179 so blocking the I-kappa-B signaling pathway and causing cell apoptosis.
- ↑ Lahtela J, Nousiainen HO, Stefanovic V, Tallila J, Viskari H, Karikoski R, Gentile M, Saloranta C, Varilo T, Salonen R, Kestilä M. Mutant CHUK and severe fetal encasement malformation. The New England journal of medicine. 2010 Oct 21; 363(17):1631-7.(Link to article – subscription may be required.)
- ↑ Spinner JL, Seo KS, O'Loughlin JL, Cundiff JA, Minnich SA, Bohach GA, Kobayashi SD. Neutrophils are resistant to Yersinia YopJ/P-induced apoptosis and are protected from ROS-mediated cell death by the type III secretion system. PloS one. 2010; 5(2):e9279.(Epub) (Link to article – subscription may be required.)