A protective role for the human SMG-1 kinase against tumor necrosis factor-alpha-induced apoptosis

Department of Experimental Therapeutics, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, Florida 33612, USA.
Journal of Biological Chemistry (Impact Factor: 4.6). 06/2008; 283(19):13174-84. DOI: 10.1074/jbc.M708008200
Source: PubMed

ABSTRACT The human suppressor of morphogenesis in genitalia-1 (hSMG-1) protein kinase plays dual roles in mRNA surveillance and genotoxic stress response pathways in human cells. Here, we report that small interfering RNA-mediated depletion of hSMG-1, but not ATM, ATR, hUpf1, or hUpf2, in human U2OS osteosarcoma cells markedly increases the magnitude and accelerates the rate of apoptosis induced by tumor necrosis factor-alpha (TNFalpha) stimulation. The increase in TNFalpha-mediated cell killing observed in hSMG-1-depleted cells is not related to the suppression of nonsense-mediated mRNA decay or to the inhibition of TNFalpha-induced NF-kappaB activation. Rather, we observed that loss of hSMG-1 accelerates the degradation of the long form of the FLICE-inhibitory protein (FLIP(L)), an inhibitor of death-inducing signaling complex-mediated caspase-8 activation, in TNFalpha-treated cells. These results suggest that hSMG-1 plays an important role in cell survival during TNFalpha-induced stress.

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May 21, 2014