Abstract:
:We have analysed the importance of proper substrate methylation by S-adenosylmethionine-dependent methyltransferases for cell survival and cell cycle progression. We show that treatment of cells with the methyltransferase inhibitor adenosine dialdehyde (AdOx) causes cell cycle arrest and death in different cell types. The phenotypical outcome and form of cell death was strikingly dependent on the AdOx concentration. Lower AdOx concentrations led to a G2 arrest and predominantly caused apoptosis, as judged by biochemical and morphological criteria. Apoptotic cell death was largely dependent on the presence of the tumour suppressor p53, but did not require the Bcl-2 family member Bax. Interestingly, higher concentrations of AdOx led to a novel and so far undescribed form of cell death, which was characterized by distinct, caspase-independent alterations of the cell shape including a marked protuberation of the nucleus, cytoplasmic extensions, actin aggregation, and incomplete chromatin condensation. Although this latter form of cell death was clearly distinguishable from apoptosis, early apoptotic features such as Bax activation were detected, indicating a commitment but incomplete execution of apoptosis. Altogether, these data show that methylation reactions play a distinct role in cell survival, which might influence the decision between different phenotypic forms of cell death.
journal_name
Oncogenejournal_title
Oncogeneauthors
Schwerk C,Schulze-Osthoff Kdoi
10.1038/sj.onc.1208855subject
Has Abstractpub_date
2005-10-27 00:00:00pages
7002-11issue
47eissn
0950-9232issn
1476-5594pii
1208855journal_volume
24pub_type
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