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Citations to this article

CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling
Petro Starokadomskyy, … , Jozef Gecz, Ezra Burstein
Petro Starokadomskyy, … , Jozef Gecz, Ezra Burstein
Published April 8, 2013
Citation Information: J Clin Invest. 2013;123(5):2244-2256. https://doi.org/10.1172/JCI66466.
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Research Article Oncology Article has an altmetric score of 13

CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling

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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.

Authors

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, Ezra Burstein

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 Total
Citations: 5 5 8 1 7 3 5 4 6 3 4 3 54
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2014 (3)

Title and authors Publication Year
Copper Metabolism Domain-containing 1 Represses Genes that Promote Inflammation and Protects Mice From Colitis and Colitis-associated Cancer
H Li, L Chan, P Bartuzi, SD Melton, A Weber, S Ben-Shlomo, C Varol, M Raetz, X Mao, P Starokadomskyy, S Sommeren, M Mokadem, H Schneider, R Weisberg, HJ Westra, T Esko, A Metspalu, V Kumar, WA Faubion, F Yarovinsky, M Hofker, C Wijmenga, M Kracht, L Franke, V Aguirre, RK Weersma, N Gluck, B de Sluis, E Burstein
Gastroenterology 2014
COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A
CA Phillips-Krawczak, A Singla, P Starokadomskyy, Z Deng, DG Osborne, H Li, CJ Dick, TS Gomez, M Koenecke, JS Zhang, H Dai, LF Sifuentes-Dominguez, LN Geng, SH Kaufmann, MY Hein, M Wallis, J McGaughran, J Gecz, B Sluis, DD Billadeau, E Burstein
Molecular biology of the cell 2014
Missense variant in CCDC22 causes X-linked recessive intellectual disability with features of Ritscher-Schinzel/3C syndrome
M Kolanczyk, P Krawitz, J Hecht, A Hupalowska, M Miaczynska, K Marschner, C Schlack, D Emerich, K Kobus, U Kornak, PN Robinson, B Plecko, G Grangl, S Uhrig, S Mundlos, D Horn
European Journal of Human Genetics 2014

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ISSN: 0021-9738 (print), 1558-8238 (online)

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