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

Title
Ubiquitin-proteasome pathway as a primary defender against TRAIL-mediated cell death
Authors
Kim S.Choi K.Kwon D.Benveniste E.N.Choi C.
Ewha Authors
최철희
Issue Date
2004
Journal Title
Cellular and Molecular Life Sciences
ISSN
1420-682XJCR Link
Citation
Cellular and Molecular Life Sciences vol. 61, no. 9, pp. 1075 - 1081
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
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-κB; however, inhibition of the NF-κB 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-κB-dependent signals.
DOI
10.1007/s00018-004-3477-5
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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