Document Detail


Uev1A, a ubiquitin conjugating enzyme variant, inhibits stress-induced apoptosis through NF-kappaB activation.
MedLine Citation:
PMID:  17041755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously shown that UEV1 is up-regulated in all tumor cell lines examined and when SV40-transformed human embryonic kidney cells undergo immortalization; however, it is unclear whether and how UEV1 plays a critical role in this process. UEV1A encodes a ubiquitin conjugating enzyme variant, which is required for Ubc13 (ubiquitin conjugating enzyme) catalyzed poly-ubiquitination of target proteins through Lys63-linked chains. One of the target proteins is NEMO/IKKgamma (nuclear factor-kappaB essential modulator/inhibitor of kappaB protein kinase), a regulatory subunit of IkappaB kinase in the NF-kappaB signaling pathway. In this report, we show that constitutive high-level expression of UEV1A alone in cultured human cells was sufficient to cause a significant increase in NF-kappaB activity as well as the expression of its target anti-apoptotic protein, Bcl-2 (B-cell leukemia/lymphoma 2). Overexpression of UEV1A also conferred prolonged cell survival under serum-deprived conditions, and protected cells against apoptosis induced by diverse stressing agents. All of the effects of Uev1A were reversible upon suppression of UEV1 expression by RNA interference. Our observations presented in this report provide evidence that Uev1A is a critical regulatory component in the NF-kappaB signaling pathway in response to environmental stresses and identify UEV1A as a potential proto-oncogene.
Authors:
Noor A Syed; Parker L Andersen; Robert C Warrington; Wei Xiao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  11     ISSN:  1360-8185     ISO Abbreviation:  Apoptosis     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-30     Completed Date:  2007-03-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2147-57     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, S7N-5E5, Canada.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis* / drug effects
Cell Survival / drug effects
Culture Media, Serum-Free
Gene Expression / drug effects
Hela Cells
Humans
Models, Biological
NF-kappa B / metabolism*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Transcription Factors / metabolism*
Tumor Necrosis Factor-alpha / pharmacology
Ubiquitin-Conjugating Enzymes / metabolism*
Chemical
Reg. No./Substance:
0/Culture Media, Serum-Free; 0/NF-kappa B; 0/Proto-Oncogene Proteins c-bcl-2; 0/Transcription Factors; 0/Tumor Necrosis Factor-alpha; EC 6.3.2.19/UBE2V1 protein, human; EC 6.3.2.19/Ubiquitin-Conjugating Enzymes

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