JBC

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


     

Originally published In Press as doi:10.1074/jbc.M103877200 on May 31, 2001

J. Biol. Chem., Vol. 276, Issue 36, 33444-33451, September 7, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/36/33444    most recent
M103877200v1
Right arrow Alert me when this article is cited
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Drewett, V.
Right arrow Articles by Shaw, P. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Drewett, V.
Right arrow Articles by Shaw, P. E.

Serum Response Factor Cleavage by Caspases 3 and 7 Linked to Apoptosis in Human BJAB Cells*

Victoria DrewettDagger , Andrew Devitt, Janice Saxton, Neil Portman, Peter Greaney, NaEun Cheong§, Teresa F. Alnemri§, Emad Alnemri§, and Peter E. Shaw

From the School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom and § Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541

Apoptosis involves the cessation of cellular processes, the breakdown of intracellular organelles, and, finally, the nonphlogistic clearance of apoptotic cells from the body. Important for these events is a family of proteases, caspases, which are activated by a proteolytic cleavage cascade and drive apoptosis by targeting key proteins within the cell. Here, we demonstrate that serum response factor (SRF), a transcription factor essential for proliferative gene expression, is cleaved by caspases and that this cleavage occurs in proliferating murine fibroblasts and can be induced in the human B-cell line BJAB. We identify the two major sites at which SRF cleavage occurs as Asp245 and Asp254, the caspases responsible for the cleavage and generate a mutant of SRF resistant to cleavage in BJAB cells. Investigation of the physiological and functional significance of SRF cleavage reveals that it correlates with the loss of c-fos expression, whereby neither SRF cleavage fragment retains transcriptional activity. Moreover, the expression of a noncleavable SRF in BJAB cells suppresses apoptosis induced by Fas cross-linking. These results suggest that for apoptosis to proceed, the transcriptional events promoting cell survival and proliferation, in which SRF is involved, must first be inactivated.

* This work was supported by the Wellcome Trust and, in part, by the Dr. Mildred Scheel Stiftung für Krebsforschung and the Max Planck Gesellschaft.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Present address: Oxford Glycoscience, The Forum, Abingdon, Oxon OX14 4RY, United Kingdom.

To whom correspondence should be addressed: School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK. Tel.: 44-115-970-9362; Fax: 44-115-970-9926; E-mail: peter.shaw@nottingham.ac.uk.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
A. Fleige, S. Alberti, L. Grobe, U. Frischmann, R. Geffers, W. Muller, A. Nordheim, and A. Schippers
Serum Response Factor Contributes Selectively to Lymphocyte Development
J. Biol. Chem., August 17, 2007; 282(33): 24320 - 24328.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Niu, W. Yu, S. X. Zhang, M. Barron, N. S. Belaguli, M. D. Schneider, M. Parmacek, A. Nordheim, and R. J. Schwartz
Conditional Mutagenesis of the Murine Serum Response Factor Gene Blocks Cardiogenesis and the Transcription of Downstream Gene Targets
J. Biol. Chem., September 16, 2005; 280(37): 32531 - 32538.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Kasza, A. O'Donnell, K. Gascoigne, L. A. H. Zeef, A. Hayes, and A. D. Sharrocks
The ETS Domain Transcription Factor Elk-1 Regulates the Expression of Its Partner Protein, SRF
J. Biol. Chem., January 14, 2005; 280(2): 1149 - 1155.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
E. R. Vickers, A. Kasza, I. A. Kurnaz, A. Seifert, L. A. H. Zeef, A. O'Donnell, A. Hayes, and A. D. Sharrocks
Ternary Complex Factor-Serum Response Factor Complex-Regulated Gene Activity Is Required for Cellular Proliferation and Inhibition of Apoptotic Cell Death
Mol. Cell. Biol., December 1, 2004; 24(23): 10340 - 10351.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
G. Paroni, M. Mizzau, C. Henderson, G. Del Sal, C. Schneider, and C. Brancolini
Caspase-dependent Regulation of Histone Deacetylase 4 Nuclear-Cytoplasmic Shuttling Promotes Apoptosis
Mol. Biol. Cell, June 1, 2004; 15(6): 2804 - 2818.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J. Chang, L. Wei, T. Otani, K. A. Youker, M. L. Entman, and R. J. Schwartz
Inhibitory Cardiac Transcription Factor, SRF-N, Is Generated by Caspase 3 Cleavage in Human Heart Failure and Attenuated by Ventricular Unloading
Circulation, July 29, 2003; 108(4): 407 - 413.
[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.