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    Cell Death Differ. 2002 Oct;9(10):1140-6.

    The C-terminal activation domain of the STAT-1 transcription factor is necessary and sufficient for stress-induced apoptosis.

    Source

    Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.

    Abstract

    It has previously been demonstrated that the STAT-1 transcription factor plays a key role in apoptosis induced by the cellular regulatory factors interferon gamma and TNF-alpha. Here we demonstrate that cells lacking STAT-1 show reduced cell death/apoptosis in response to stressful stimuli such as heat or ischaemia. Expression of STAT-1 in these cells does not enhance basal cell death but restores sensitivity to stress-induced death whereas this effect is not observed upon over-expression of STAT-3. Enhanced sensitivity to stress-induced cell death requires the C-terminal activation domain of STAT-1 and the phosphorylation sites at tyrosine 701 and serine 727. Moreover, we show for the first time in any system that the isolated C-terminal domain of STAT-1 is able to enhance stress-induced cell death in the absence of the DNA binding domain or any other region of STAT-1. Hence, STAT-1 plays a key role in stress-induced cell death, potentially acting via a novel co-activator-type mechanism and represents a possible therapeutic target for strategies aimed at minimising cell death, for example, following ischaemic injury.

    PMID:
    12232802
    [PubMed - indexed for MEDLINE]
    Free full text

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