Characterization of cytoplasmic Caspase-2 activation by induced proximity

Bouchier-Hayes, L., Oberst, A., McStay, G.P., Connell, S., Tait, S.W.G. , Beere, H.M. and Green, D.R. (2009) Characterization of cytoplasmic Caspase-2 activation by induced proximity. Molecular Cell, 35(6), pp. 830-840. (doi: 10.1016/j.molcel.2009.07.023)

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Publisher's URL: http://dx.doi.org/10.1016/j.molcel.2009.07.023

Abstract

Caspase-2 is an initiator caspase activated in response to heat shock and other stressors that induce apoptosis. Activation of caspase-2 requires induced proximity resulting after recruitment to caspase-2 activation complexes such as the PIDDosome. We have adapted bimolecular fluorescence complementation (BiFC) to measure caspase-2 induced proximity in real time in single cells. Nonfluorescent fragments of the fluorescent protein Venus that can associate to reform the fluorescent complex were fused to caspase-2, allowing visualization and kinetic measurements of caspase-2 induced proximity after heat shock and other stresses. This revealed that the caspase-2 activation platform occurred in the cytosol and not in the nucleus in response to heat shock, DNA damage, cytoskeletal disruption, and other treatments. Activation, as measured by this approach, in response to heat shock was RAIDD dependent and upstream of mitochondrial outer-membrane permeabilization. Furthermore, we identify Hsp90α as a key negative regulator of heat shock-induced caspase-2 activation

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:UNSPECIFIED
Authors: Bouchier-Hayes, L., Oberst, A., McStay, G.P., Connell, S., Tait, S.W.G., Beere, H.M., and Green, D.R.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Molecular Cell
Journal Abbr.:Mol Cell
ISSN:1097-2765
ISSN (Online):1097-4164

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