HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 52, 39741-39745, December 29, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/52/39741    most recent R600033200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Young, S. G. Articles by Fong, L. G. Search for Related Content PubMed PubMed Citation Articles by Young, S. G. Articles by Fong, L. G. Social Bookmarking                      What's this?

Minireview

Prelamin A Farnesylation and Progeroid Syndromes^*

From the Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095

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.

^* This minireview will be reprinted in the 2006 Minireview Compendium, which will be available in January, 2007. This work was supported by National Institutes of Health Grants AR050200 and HL76839 (to S. G. Y.), AR050966 (to M. M.), and HL086683 (to L. G. F.), grants from the Progeria Research Foundation (to S. G. Y. and L. G. F.), and a grant-in-aid from the American Heart Association, Western States Affiliate (to L. G. F.).

¹ To whom correspondence may be addressed. E-mail: sgyoung{at}mednet.ucla.edu. ² To whom correspondence may be addressed. E-mail: lfong{at}mednet.ucla.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Barrowman, C. Hamblet, C. M. George, and S. Michaelis Analysis of Prelamin A Biogenesis Reveals the Nucleus to be a CaaX Processing Compartment Mol. Biol. Cell, December 1, 2008; 19(12): 5398 - 5408. [Abstract] [Full Text] [PDF]

				Y. Wang, A. A. Panteleyev, D. M. Owens, K. Djabali, C. L. Stewart, and H. J. Worman Epidermal expression of the truncated prelamin A causing Hutchinson-Gilford progeria syndrome: effects on keratinocytes, hair and skin Hum. Mol. Genet., August 1, 2008; 17(15): 2357 - 2369. [Abstract] [Full Text] [PDF]

				E. Meshorer and Y. Gruenbaum Gone with the Wnt/Notch: stem cells in laminopathies, progeria, and aging J. Cell Biol., April 3, 2008; 181(1): 9 - 13. [Abstract] [Full Text] [PDF]

				K. Gehrig, R. B. Cornell, and N. D. Ridgway Expansion of the Nucleoplasmic Reticulum Requires the Coordinated Activity of Lamins and CTP:Phosphocholine Cytidylyltransferase {alpha} Mol. Biol. Cell, January 1, 2008; 19(1): 237 - 247. [Abstract] [Full Text] [PDF]

				M. W. Kieran, L. Gordon, and M. Kleinman New Approaches to Progeria Pediatrics, October 1, 2007; 120(4): 834 - 841. [Abstract] [Full Text] [PDF]

				S. G. Clarke HIV protease inhibitors and nuclear lamin processing: Getting the right bells and whistles PNAS, August 28, 2007; 104(35): 13857 - 13858. [Full Text] [PDF]

				R. A. Hegele, T. R. Joy, S. A. Al-Attar, and B. K. Rutt Thematic review series: Adipocyte Biology. Lipodystrophies: windows on adipose biology and metabolism J. Lipid Res., July 1, 2007; 48(7): 1433 - 1444. [Abstract] [Full Text] [PDF]