English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  CCDC22 deficiency in humans blunts activation of proinflammatory NF-kappaB signaling

Starokadomskyy, P., Gluck, N., Li, H., Chen, B., Wallis, M., Maine, G. N., et al. (2013). CCDC22 deficiency in humans blunts activation of proinflammatory NF-kappaB signaling. The Journal of Clinical Investigation, 123(5), 2244-2256. doi:10.1172/JCI66466.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0018-EA7A-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0018-EA82-1
Genre: Journal Article

Files

show Files
hide Files
:
Starokadomskyy.pdf (Publisher version), 4MB
Name:
Starokadomskyy.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2013, American Society for Clinical Investigation
License:
-

Locators

show

Creators

show
hide
 Creators:
Starokadomskyy, P., Author
Gluck, N., Author
Li, H., Author
Chen, B., Author
Wallis, M., Author
Maine, G. N., Author
Mao, X., Author
Zaidi, I. W., Author
Hein, M. Y., Author
McDonald, F. J., Author
Lenzner, S.1, Author
Zecha, A., Author
Ropers, H. H.1, Author              
Kuss, A. W.2, Author              
McGaughran, J., Author
Gecz, J., Author
Burstein, E., Author
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 73, 14195 Berlin, Germany, ou_1433549              
2Familial Cognitive Disorders (Luciana Musante), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr, 73, 14195 Berlin, Germany, ou_1479644              

Content

show
hide
Free keywords: Adaptor Proteins, Signal Transducing/metabolism Carrier Proteins/*metabolism Chromosomes, Human, X Ectodermal Dysplasia/metabolism *Gene Expression Regulation Genetic Linkage HEK293 Cells HeLa Cells Humans I-kappa B Proteins/metabolism Inflammation Microscopy, Fluorescence Mutation NF-kappa B/*metabolism Neoplasms/metabolism Protein Structure, Tertiary Proteins/*metabolism *Signal Transduction Ubiquitin/metabolism
 Abstract: NF-kappaB 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 IkappaB proteins. In addition, the inactivation of DNA-bound NF-kappaB 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-kappaB blockade. Indeed, patient-derived cells demonstrated impaired NF-kappaB activation due to decreased IkappaB ubiquitination and degradation. In addition, we found that COMMD8 acted in conjunction with CCDC22 to direct the degradation of IkappaB proteins. Taken together, our results indicate that CCDC22 participates in NF-kappaB activation and that its deficiency leads to decreased IkappaB turnover in humans, highlighting an important regulatory component of this pathway.

Details

show
hide
Language(s): eng - English
 Dates: 2013-04-082013-05-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1172/JCI66466
ISSN: 1558-8238 (Electronic)0021-9738 (Print)
URI: http://www.ncbi.nlm.nih.gov/pubmed/23563313
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: The Journal of Clinical Investigation
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York, NY : American Society for Clinical Investigation
Pages: - Volume / Issue: 123 (5) Sequence Number: - Start / End Page: 2244 - 2256 Identifier: ISSN: 0021-9738
CoNE: https://pure.mpg.de/cone/journals/resource/954926940717_2