Serum response factor cleavage by caspases 3 and 7 linked to apoptosis in human BJAB cells

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

Research output: Contribution to journalArticle

Abstract

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 e-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.

Original languageEnglish
Pages (from-to)33444-33451
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number36
Early online date31 May 2001
DOIs
Publication statusPublished - 7 Sep 2001

Bibliographical note

This research was originally published in the Journal of Biological Chemistry. Victoria Drewett, Andrew Devitt, Janice Saxton, Neil Portman, Peter Greaney, NaEun Cheong, Teresa F. Alnemri, Emad Alnemri and Peter E. Shaw. Serum Response Factor Cleavage by Caspases 3 and 7 Linked to Apoptosis in Human BJAB Cells. J. Biol. Chem. 2001; Vol 276:33444-33451. © the American Society for Biochemistry and Molecular Biology

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    Drewett, V., Devitt, A., Saxton, J., Portman, N., Greaney, P., Cheong, N., Alnemri, T. F., Alnemri, E., & Shaw, P. E. (2001). Serum response factor cleavage by caspases 3 and 7 linked to apoptosis in human BJAB cells. Journal of Biological Chemistry, 276(36), 33444-33451. https://doi.org/10.1074/jbc.M103877200