
<ArticleTitle>Serum response factor cleavage by <prot><prot>caspases 3</prot> and 7</prot> linked to apoptosis in human BJAB cells.</ArticleTitle>
<AbstractText>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 <prot>serum response factor</prot> (<prot>SRF</prot>), 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 <prot>SRF</prot> cleavage occurs as Asp(245) and Asp(254), the caspases responsible for the cleavage and generate a mutant of <prot>SRF</prot> resistant to cleavage in BJAB cells. Investigation of the physiological and functional significance of <prot>SRF</prot> cleavage reveals that it correlates with the loss of <prot>c-fos</prot> expression, whereby neither <prot>SRF</prot> cleavage fragment retains transcriptional activity. Moreover, the expression of a noncleavable <prot>SRF</prot> in BJAB cells suppresses apoptosis induced by <prot>Fas</prot> cross-linking. These results suggest that for apoptosis to proceed, the transcriptional events promoting cell survival and proliferation, in which <prot>SRF</prot> is involved, must first be inactivated.</AbstractText>
