Cdk2 activation acts upstream of the mitochondrion during glucocorticoid induced thymocyte apoptosis

European Journal of Immunology
Francesc GranésG Gil-Gómez

Abstract

Thymocytes undergo apoptosis during negative selection in vivo and following treatment with glucocorticoids or DNA-damaging drugs in vitro. The post-mitochondrial biochemical steps leading to apoptosis induced by these stimuli are well characterized, however, much less is known about the pathways connecting receptor triggering, apical caspase activation and induction of mitochondrial dysfunction. These stimuli specifically activate the kinase Cdk2 and this step is obligatory for these forms of thymocyte apoptosis. We report here that Cdk2 activation is a very early step during thymocyte apoptosis preceding apical caspase activation and phosphatidylserine exposure. Furthermore, Cdk2 activation is required for mitochondrial permeability disruption, cytochrome c release and, as a consequence, activation of the downstream caspases 9 and 3. Our data allow an integrated linear pathway regulating DNA damage and glucocorticoid-induced thymocyte apoptosis to be proposed.

Citations

Oct 18, 2008·Cell Death and Differentiation·M B RoigG Gil-Gómez
Sep 5, 2009·Cell Death and Differentiation·M J WoodwardH J M Brady
Jan 14, 2010·The Journal of Biological Chemistry·Ling XueAstar Winoto
Jan 5, 2006·The Journal of Experimental Medicine·Ronit Vogt SionovEitan Yefenof
May 9, 2007·Molecular and Cellular Biology·Cyril BerthetPhilipp Kaldis
Mar 9, 2018·The Journal of Experimental Medicine·Tal TeitzJian Zuo
Nov 27, 2016·Apoptosis : an International Journal on Programmed Cell Death·Lilla PrenekTimea Berki
Dec 14, 2018·Journal of Medicinal Chemistry·Solomon TadesseShudong Wang

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