Methyltransferase inhibition induces p53-dependent apoptosis and a novel form of cell death.

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

Oncogene

journal_title

Oncogene

authors

Schwerk C,Schulze-Osthoff K

doi

10.1038/sj.onc.1208855

subject

Has Abstract

pub_date

2005-10-27 00:00:00

pages

7002-11

issue

47

eissn

0950-9232

issn

1476-5594

pii

1208855

journal_volume

24

pub_type

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