Document Detail


Prelamin A farnesylation and progeroid syndromes.
MedLine Citation:
PMID:  17090536     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hutchinson-Gilford progeria syndrome (HGPS) is caused by a LMNA mutation that leads to the synthesis of a mutant prelamin A that is farnesylated but cannot be further processed to mature lamin A. A more severe progeroid disorder, restrictive dermopathy (RD), is caused by the loss of the prelamin A-processing enzyme, ZMPSTE24. The absence of ZMPSTE24 prevents the endoproteolytic processing of farnesyl-prelamin A to mature lamin A and leads to the accumulation of farnesyl-prelamin A. In both HGPS and RD, the farnesyl-prelamin A is targeted to the nuclear envelope, where it interferes with the integrity of the nuclear envelope and causes misshapen cell nuclei. Recent studies have shown that the frequency of misshapen nuclei can be reduced by treating cells with a farnesyltransferase inhibitor (FTI). Also, administering an FTI to mouse models of HGPS and RD ameliorates the phenotypes of progeria. These studies have prompted interest in testing the efficacy of FTIs in children with HGPS.
Authors:
Stephen G Young; Margarita Meta; Shao H Yang; Loren G Fong
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2006-11-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-25     Completed Date:  2007-02-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  39741-5     Citation Subset:  IM    
Affiliation:
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA. sgyoung@mednet.ucla.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Humans
Nuclear Proteins / chemistry,  genetics,  metabolism*,  physiology
Progeria / etiology,  genetics,  metabolism*,  pathology
Protein Precursors / chemistry,  genetics,  metabolism*,  physiology
Protein Prenylation / genetics
Syndrome
Grant Support
ID/Acronym/Agency:
AR050200/AR/NIAMS NIH HHS; AR050966/AR/NIAMS NIH HHS; HL086683/HL/NHLBI NIH HHS; HL76839/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 0/Protein Precursors; 0/prelamin A

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


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