Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: CCDC22 deficiency in humans blunts activation of proinfammatory NF-KappaB signaling
Author: Starokadomskyy, P.
Gluck, N.
Li, H.
Chen, B.
Wallis, M.
Maine, G.
Mao, X.
Zaidi, I.
Hein, M.
McDonald, F.
Lenzner, S.
Zecha, A.
Ropers, H.
Kuss, A.
McGaughran, J.
Gecz, J.
Burstein, E.
Citation: Journal of Clinical Investigation, 2013; 123(5):2244-2256
Publisher: Amer Soc Clinical Investigation Inc
Issue Date: 2013
ISSN: 0021-9738
Statement of
Petro Starokadomskyy, Nathan Gluck, Haiying Li, Baozhi Chen, Mathew Wallis, Gabriel N. Maine, Xicheng Mao, Iram W. Zaidi, Marco Y. Hein, Fiona J. McDonald, Steffen Lenzner, Agnes Zecha, Hans-Hilger Ropers, Andreas W. Kuss, Julie McGaughran, Jozef Gecz, and Ezra Burstein
Abstract: NF-κB is a master regulator of inflammation and has been implicated in the pathogenesis of immune disorders and cancer. Its regulation involves a variety of steps, including the controlled degradation of inhibitory IκB proteins. In addition, the inactivation of DNA-bound NF-κB is essential for its regulation. This step requires a factor known as copper metabolism Murr1 domain–containing 1 (COMMD1), the prototype member of a conserved gene family. While COMMD proteins have been linked to the ubiquitination pathway, little else is known about other family members. Here we demonstrate that all COMMD proteins bind to CCDC22, a factor recently implicated in X-linked intellectual disability (XLID). We showed that an XLID-associated CCDC22 mutation decreased CCDC22 protein expression and impaired its binding to COMMD proteins. Moreover, some affected individuals displayed ectodermal dysplasia, a congenital condition that can result from developmental NF-κB blockade. Indeed, patient-derived cells demonstrated impaired NF-κB activation due to decreased IκB ubiquitination and degradation. In addition, we found that COMMD8 acted in conjunction with CCDC22 to direct the degradation of IκB proteins. Taken together, our results indicate that CCDC22 participates in NF-κB activation and that its deficiency leads to decreased IκB turnover in humans, highlighting an important regulatory component of this pathway.
Keywords: Hela Cells
Chromosomes, Human, X
Ectodermal Dysplasia
Adaptor Proteins, Signal Transducing
Carrier Proteins
NF-kappa B
Microscopy, Fluorescence
Signal Transduction
Gene Expression Regulation
Protein Structure, Tertiary
I-kappa B Proteins
Genetic Linkage
HEK293 Cells
NF-KappaB Inhibitor alpha
Rights: Copyright © 2013, American Society for Clinical Investigation
DOI: 10.1172/JCI66466
Published version:
Appears in Collections:Aurora harvest
Paediatrics publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.