ATM kinase promotes both caspase-8 and caspase-9 activation during TNF-alpha-induced apoptosis of HeLa cells

Abstract

In this study, we show that atraxia telangiectasia mutated kinase (ATM) activity is generally upregulated by different apoptotic stimuli, i.e. TNF-alpha, TRAIL, paclitaxel, or UV. Apoptotic progression is markedly attenuated by siATM-RNA through down regulation of caspase-8 and caspase-9 in parallel with decreases in FLIP-S (short form of cellular FLICE inhibitory protein) protein levels and Bid cleavage. In addition, ATM activity is upregulated through t-Cdc6 while caspase-8 and caspase-9 activities increase. Taken together, we suggest that ATM regulates caspase-8 activation by influencing levels of FLIP-S, ATM kinase activity is upregulated by t-Cdc6, and increased ATM activity plays an essential role in the amplification of apoptosis in TNF-alpha-stimulated HeLa cells. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.