Ubiquitin-proteasome pathway as a primary defender against TRAIL-mediated cell death

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptotic cell death as well as expression of proinflammatory genes such as CXCL8 in malignant human astrocytoma cells. However, the molecular mechanisms that determine the fate of cells are not yet understood. The ubiquitin (Ub)-proteasome pathway regulates a wide range of cellular functions through degradation of various regulatory proteins; given this, we hypothesized that this pathway may play a central role in TRAIL-mediated signaling. We demonstrate here that inhibition of the Ub-proteasome pathway enhanced TRAIL-mediated cell death of human astrocytoma CRT-MG cells within hours by blocking degradation of active caspase-8 and -3. Proteasome inhibitors suppressed TRAIL-mediated activation of NF-kappaB; however, inhibition of the NF-kappaB pathway alone was not sufficient to enhance TRAIL-mediated cell death. Collectively, these results suggest that the Ub-proteasome pathway may play an important role as an antiapoptotic surveillance system by eliminating activated caspases as well as mediating NF-kappaB-dependent signals.
Publisher
BIRKHAUSER VERLAG AG
Issue Date
2004-04
Language
English
Article Type
Article
Keywords

PROTEIN LIGASE ACTIVITY; INHIBITOR PS-341; APOPTOSIS; DEGRADATION; EXPRESSION; ACTIVATION; GLIOMA; KINASE

Citation

CELLULAR AND MOLECULAR LIFE SCIENCES, v.61, pp.1075 - 1081

ISSN
1420-682X
DOI
10.1007/s00018-004-3477-5
URI
http://hdl.handle.net/10203/82728
Appears in Collection
BiS-Journal Papers(저널논문)
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