De Luca A#, R. De Maria*, A. Baldi#, R. Trotta#, F. Facchiano#, A. Giordano#, R. Testi* and G. Condorelli#

#Department of Pathology, Anatomy, and Cell Biology, Sbarro Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Philadelphia, Pennsylvania, USA and *Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata".

Corresponding Author: Gianluigi Condorelli

Recent evidence suggested a role for the cell cycle dependent kinases cdc2 and cdk2 in apoptosis. An important mechanism by which many cell types could undergo apoptosis is through the activation of the Fas molecule on the cell membrane. To investigate whether Fas-induced cell death activated cdc2 and cdk2 kinases inappropriately, the human T lymphoma cells HUT-78, which express a high copy number of Fas, and two other previously characterized subclones of the same cell line which express mutant, cell death-deficient dominant-negative forms of Fas, were Fas-challenged and the changes in cdc2 and cdk2 kinase activity monitored. In both wild-type and Fas-mutated HUT-78 cells, apoptosis was associated simultaneously with decreased cdc2 and increased cdk2 activity. This association suggested that changes in cdc2 and cdk2 kinase activity are secondary events in cell death mediated by Fas.