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

Vasco Oliveira, William J. Romanow, Christoph Geisen, Diane M. Otterness, Frank Mercurio, Gang Wang Hong, William S. Dalton, Robert T. Abraham

Research output: Contribution to journalArticle

35 Citations (Scopus)

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-α (TNFα) stimulation. The increase in TNFα-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 TNFα-induced NF-κB activation. Rather, we observed that loss of hSMG-1 accelerates the degradation of the long form of the FLICE-inhibitory protein (FLIPL), an inhibitor of death-inducing signaling complex-mediated caspase-8 activation, in TNFα-treated cells. These results suggest that hSMG-1 plays an important role in cell survival during TNFα-induced stress.

Original languageEnglish (US)
Pages (from-to)13174-13184
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number19
DOIs
StatePublished - May 9 2008

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Genitalia
Tumor Necrosis Factor-alpha
Morphogenesis
Apoptosis
Cells
Death Domain Receptor Signaling Adaptor Proteins
CASP8 and FADD-Like Apoptosis Regulating Protein
Chemical activation
Messenger RNA
Caspase 8
Automatic teller machines
Nonsense Mediated mRNA Decay
Protein Kinases
Small Interfering RNA
Osteosarcoma
human SMG1 protein
DNA Damage
Degradation
Cell Survival

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Oliveira, V., Romanow, W. J., Geisen, C., Otterness, D. M., Mercurio, F., Hong, G. W., ... Abraham, R. T. (2008). A protective role for the human SMG-1 kinase against tumor necrosis factor-α-induced apoptosis. Journal of Biological Chemistry, 283(19), 13174-13184. https://doi.org/10.1074/jbc.M708008200
Oliveira, Vasco ; Romanow, William J. ; Geisen, Christoph ; Otterness, Diane M. ; Mercurio, Frank ; Hong, Gang Wang ; Dalton, William S. ; Abraham, Robert T. / A protective role for the human SMG-1 kinase against tumor necrosis factor-α-induced apoptosis. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 19. pp. 13174-13184.
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Oliveira, V, Romanow, WJ, Geisen, C, Otterness, DM, Mercurio, F, Hong, GW, Dalton, WS & Abraham, RT 2008, 'A protective role for the human SMG-1 kinase against tumor necrosis factor-α-induced apoptosis', Journal of Biological Chemistry, vol. 283, no. 19, pp. 13174-13184. https://doi.org/10.1074/jbc.M708008200

A protective role for the human SMG-1 kinase against tumor necrosis factor-α-induced apoptosis. / Oliveira, Vasco; Romanow, William J.; Geisen, Christoph; Otterness, Diane M.; Mercurio, Frank; Hong, Gang Wang; Dalton, William S.; Abraham, Robert T.

In: Journal of Biological Chemistry, Vol. 283, No. 19, 09.05.2008, p. 13174-13184.

Research output: Contribution to journalArticle

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