Document Detail


Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD.
MedLine Citation:
PMID:  17981138     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Spermatogenesis involves an early wave of germ cell apoptosis, which is required for maintaining the balance between germ cells and supporting Sertoli cells. However, the signaling mechanism regulating this apoptotic event is poorly defined. Here we show that genetic deficiency of Cyld, a recently identified deubiquitinating enzyme, attenuates the early wave of germ cell apoptosis and causes impaired spermatogenesis in mice. Interestingly, the loss of CYLD in testicular cells leads to activation of the transcription factor NF-kappaB and aberrant expression of antiapoptotic genes. We further show that CYLD negatively regulates a ubiquitin-dependent NF-kappaB activator, RIP1. CYLD binds to RIP1 and inhibits its ubiquitination and signaling function. These findings establish CYLD as a pivotal deubiquitinating enzyme (DUB) that regulates germ cell apoptosis and spermatogenesis and suggest an essential role for CYLD in controlling the RIP1/NF-kappaB signaling axis in testis.
Authors:
Ato Wright; William W Reiley; Mikyoung Chang; Wei Jin; Andrew Joon Lee; Minying Zhang; Shao-Cong Sun
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Developmental cell     Volume:  13     ISSN:  1534-5807     ISO Abbreviation:  Dev. Cell     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-05     Completed Date:  2008-02-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  705-16     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Cysteine Endopeptidases / genetics,  physiology*
GTPase-Activating Proteins / metabolism
Germ Cells / physiology*
Mice
Mice, Knockout
NF-kappa B / metabolism
Phosphorylation
Signal Transduction
Spermatogenesis*
Ubiquitination
Grant Support
ID/Acronym/Agency:
AI057555/AI/NIAID NIH HHS; AI064639/AI/NIAID NIH HHS; CA94922/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/GTPase-Activating Proteins; 0/NF-kappa B; 0/Ralbp1 protein, mouse; EC 3.1.2.15/CYLD protein, mouse; EC 3.4.22.-/Cysteine Endopeptidases
Comments/Corrections
Comment In:
Dev Cell. 2007 Nov;13(5):601-3   [PMID:  17981127 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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