Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M102908200 on June 8, 2001

J. Biol. Chem., Vol. 276, Issue 31, 29051-29058, August 3, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/31/29051    most recent
M102908200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Leung, G. K.
Right arrow Articles by Young, S. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leung, G. K.
Right arrow Articles by Young, S. G.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Biochemical Studies of Zmpste24-deficient Mice*

Gordon K. LeungDagger §||, Walter K. Schmidt||**, Martin O. BergoDagger §||, Bryant GavinoDagger , Darren H. WongDagger Dagger , Amy Tam**, Matthew N. AshbyDagger , Susan Michaelis**, and Stephen G. YoungDagger §§§

From the Dagger  Gladstone Institute of Cardiovascular Disease, § Cardiovascular Research Institute, and  Department of Medicine, University of California, San Francisco, California 94141-9100, the ** Department of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and Dagger Dagger  Axys Pharmaceuticals, South San Francisco, California 94080

Genetic studies in Saccharomyces cerevisiae identified two genes, STE24 and RCE1, involved in cleaving the three carboxyl-terminal amino acids from isoprenylated proteins that terminate with a CAAX sequence motif. Ste24p cleaves the carboxyl-terminal "-AAX" from the yeast mating pheromone a-factor, whereas Rce1p cleaves the -AAX from both a-factor and Ras2p. Ste24p also cleaves the amino terminus of a-factor. The mouse genome contains orthologues for both yeast RCE1 and STE24. We previously demonstrated, with a gene-knockout experiment, that mouse Rce1 is essential for development and that Rce1 is entirely responsible for the carboxyl-terminal proteolytic processing of the mouse Ras proteins. In this study, we cloned mouse Zmpste24, the orthologue for yeast STE24 and showed that it could promote a-factor production when expressed in yeast. Then, to assess the importance of Zmpste24 in development, we generated Zmpste24-deficient mice. Unlike the Rce1 knockout mice, Zmpste24-deficient mice survived development and were fertile. Since no natural substrates for mammalian Zmpste24 have been identified, yeast a-factor was used as a surrogate substrate to investigate the biochemical activities in membranes from the cells and tissues of Zmpste24-deficient mice. We demonstrate that Zmpste24-deficient mouse membranes, like Ste24p-deficient yeast membranes, have diminished CAAX proteolytic activity and lack the ability to cleave the amino terminus of the a-factor precursor. Thus, both enzymatic activities of yeast Ste24p are conserved in mouse Zmpste24, but these enzymatic activities are not essential for mouse development or for fertility.

* This work was supported in part by National Institutes of Health Grants HL41633 and AG15451 (to S. G. Y.) and GM41223 (to S. M.), a Howard Hughes Medical Institute Postdoctoral Fellowship for Physicians (to G. K. L.), and grant awards from the University of California Tobacco-related Disease Research Program (to M. O. B. and S. G. Y.).

|| Contributed equally to the results of this work.

§§ To whom reprint requests should be addressed: Gladstone Institute of Cardiovascular Disease, P. O. Box 419100, San Francisco, CA 94141-9100. Tel.: 415-695-3774; Fax: 415-285-5632; E-mail: syoung@ gladstone.ucsf.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 ScienceHome page
S. Ricardo and R. Lehmann
An ABC Transporter Controls Export of a Drosophila Germ Cell Attractant
Science, February 13, 2009; 323(5916): 943 - 946.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Coffinier, S. E. Hudon, R. Lee, E. A. Farber, C. Nobumori, J. H. Miner, D. A. Andres, H. P. Spielmann, C. A. Hrycyna, L. G. Fong, et al.
A Potent HIV Protease Inhibitor, Darunavir, Does Not Inhibit ZMPSTE24 or Lead to an Accumulation of Farnesyl-prelamin A in Cells
J. Biol. Chem., April 11, 2008; 283(15): 9797 - 9804.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Coffinier, S. E. Hudon, E. A. Farber, S. Y. Chang, C. A. Hrycyna, S. G. Young, and L. G. Fong
From the Cover: HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells
PNAS, August 14, 2007; 104(33): 13432 - 13437.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. L. Kilpatrick and J. D. Hildebrandt
Sequence Dependence and Differential Expression of G{gamma}5 Subunit Isoforms of the Heterotrimeric G Proteins Variably Processed after Prenylation in Mammalian Cells
J. Biol. Chem., May 11, 2007; 282(19): 14038 - 14047.
[Abstract] [Full Text] [PDF]

Home page
 GENES CELLSHome page
R. Ukekawa, K. Miki, M. Fujii, H. Hirano, and D. Ayusawa
Accumulation of multiple forms of lamin A with down-regulation of FACE-1 suppresses growth in senescent human cells
Genes Cells, March 1, 2007; 12(3): 397 - 406.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. G. Young, M. Meta, S. H. Yang, and L. G. Fong
Prelamin A Farnesylation and Progeroid Syndromes
J. Biol. Chem., December 29, 2006; 281(52): 39741 - 39745.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
G. Huyer, A. Kistler, F. J. Nouvet, C. M. George, M. L. Boyle, and S. Michaelis
Saccharomyces cerevisiae a-Factor Mutants Reveal Residues Critical for Processing, Activity, and Export.
Eukaryot. Cell, September 1, 2006; 5(9): 1560 - 1570.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
A. E. Rusinol and M. S. Sinensky
Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors.
J. Cell Sci., August 15, 2006; 119(Pt 16): 3265 - 3272.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
S. G. Young, L. G. Fong, and S. Michaelis
Thematic Review Series: Lipid Posttranslational Modifications. Prelamin A, Zmpste24, misshapen cell nuclei, and progeria--new evidence suggesting that protein farnesylation could be important for disease pathogenesis
J. Lipid Res., December 1, 2005; 46(12): 2531 - 2558.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
A. Yamashita, R. Kamata, N. Kawagishi, H. Nakanishi, H. Suzuki, T. Sugiura, and K. Waku
Roles of C-Terminal Processing, and Involvement in Transacylation Reaction of Human Group IVC Phospholipase A2 (cPLA2{gamma})
J. Biochem., May 1, 2005; 137(5): 557 - 567.
[Abstract] [Full Text] [PDF]

Home page
 Sci Aging Knowl EnvironHome page
Zmpste24-/- Mice
Sci. Aging Knowl. Environ., January 12, 2005; 2005(2): tg1 - tg1.
[Full Text]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. G. Fong, J. K. Ng, M. Meta, N. Cote, S. H. Yang, C. L. Stewart, T. Sullivan, A. Burghardt, S. Majumdar, K. Reue, et al.
Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice
PNAS, December 28, 2004; 101(52): 18111 - 18116.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
A. Muchir and H. J. Worman
The Nuclear Envelope and Human Disease
Physiology, October 1, 2004; 19(5): 309 - 314.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. O. Bergo, H. D. Lieu, B. J. Gavino, P. Ambroziak, J. C. Otto, P. J. Casey, Q. M. Walker, and S. G. Young
On the Physiological Importance of Endoproteolysis of CAAX Proteins: HEART-SPECIFIC RCE1 KNOCKOUT MICE DEVELOP A LETHAL CARDIOMYOPATHY
J. Biol. Chem., February 6, 2004; 279(6): 4729 - 4736.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. O. Bergo, B. Gavino, J. Ross, W. K. Schmidt, C. Hong, L. V. Kendall, A. Mohr, M. Meta, H. Genant, Y. Jiang, et al.
Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect
PNAS, October 1, 2002; 99(20): 13049 - 13054.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Bracha, M. Lavy, and S. Yalovsky
The Arabidopsis AtSTE24 Is a CAAX Protease with Broad Substrate Specificity
J. Biol. Chem., August 9, 2002; 277(33): 29856 - 29864.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Tam, W. K. Schmidt, and S. Michaelis
The Multispanning Membrane Protein Ste24p Catalyzes CAAX Proteolysis and NH2-terminal Processing of the Yeast a-Factor Precursor
J. Biol. Chem., December 7, 2001; 276(50): 46798 - 46806.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement