Document Detail


The JAMM motif of human deubiquitinase Poh1 is essential for cell viability.
MedLine Citation:
PMID:  17237285     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Poh1 deubiquitinase activity is required for proteolytic processing of polyubiquitinated substrates by the 26S proteasome, linking deubiquitination to complete substrate degradation. Poh1 RNA interference (RNAi) in HeLa cells resulted in a reduction in cell viability and an increase in polyubiquitinated protein levels, supporting the link between Poh1 and the ubiquitin proteasome pathway. To more specifically test for any requirement of the zinc metalloproteinase motif of Poh1 to support cell viability and proteasome function, we developed a RNAi complementation strategy. Effects on cell viability and proteasome activity were assessed in cells with RNAi of endogenous Poh1 and induced expression of wild-type Poh1 or a mutant form of Poh1, in which two conserved histidines of the proposed catalytic site were replaced with alanines. We show that an intact zinc metalloproteinase motif is essential for cell viability and 26S proteasome function. As a required enzymatic component of the proteasome, Poh1 is an intriguing therapeutic drug target for cancer.
Authors:
Melissa Gallery; Jonathan L Blank; Yinghui Lin; Juan A Gutierrez; Jacqueline C Pulido; David Rappoli; Sunita Badola; Mark Rolfe; Kyle J Macbeth
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  6     ISSN:  1535-7163     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-22     Completed Date:  2007-03-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  262-8     Citation Subset:  IM    
Affiliation:
Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, MA 02139, USA. kyle.macbeth@mpi.com
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs
Cell Survival
Hela Cells
Humans
Mutant Proteins / metabolism
Proteasome Endopeptidase Complex / chemistry*,  deficiency,  metabolism*
RNA Interference
Trans-Activators / chemistry*,  deficiency,  metabolism*
Ubiquitin / metabolism*
Chemical
Reg. No./Substance:
0/Mutant Proteins; 0/PSMD14 protein, human; 0/Trans-Activators; 0/Ubiquitin; EC 3.4.25.1/Proteasome Endopeptidase Complex; EC 3.4.99.-/ATP dependent 26S protease

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


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