Abstract
Apoptosis has recently been hypothesized to be the result of aberrant cell cycle control. In this study, we have investigated the role of cell cycle-regulatory elements in Fas-induced apoptosis of hematopoietic cells. When HL-60 cells were treated with anti-Fas antibody, rapid activation of growth-associated histone H1 kinase was observed without any change in cell cycle distribution. This was accompanied by the increase in cdc2 mRNA expression and Cdc2 kinase activity. Up-regulation of cdc2 mRNA was similarly induced in BCL-2-overexpressing HL-60 subline by anti-Fas treatment independently of the appearance of apoptotic phenotypes. Fas-induced apoptosis was completely inhibited by butyrolactone I, a specific inhibitor of Cdc2 kinase. Moreover, the same phenomenon was observed during Fas-induced but not spontaneous apoptosis of postmitotic granulocytes. Finally, we have found that "Fas-responsive element" was located between nucleotides -730 and -552 of the cdc2 promoter and was responsive for transcriptional activation of the cdc2 gene during Fas-induced apoptosis. These results indicate that aberrant activation of Cdc2 is associated with Fas-induced apoptosis of hematopoietic cells, and that the mechanism of cdc2 transcription during Fas-induced apoptosis is different from that in normal cell cycle control.
Highlights
Apoptosis is the physiological process of cell death that functions to control cell populations in many aspects of the biological events
We have recently found that HL-60 cells in S phase of the cell cycle are more susceptible to apoptosis induced by various stimuli than those arrested in G0/G1 phase [17]
Apoptosis shares a number of morphological features with mitosis, including lamin disassembly and chromatin condensation, that are known to be regulated by Cdc2 kinase [12, 13]
Summary
Apoptosis is the physiological process of cell death that functions to control cell populations in many aspects of the biological events. In accordance with the increase in Fas-induced apoptotic cell death, histone H1 kinase activity was significantly enhanced in HL-60 cells by pretreatment with IFN-␥ (Fig. 2B).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
