TRIM13 regulates caspase-8 ubiquitination, translocation to autophagosomes and activation during ER stress induced cell death.
Biochim Biophys Acta
; 1833(12): 3134-3144, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24021263
ABSTRACT
The emerging evidences suggest that endoplasmic (ER) stress is involved in onset of many pathological conditions like cancer and neurodegeneration. The persistent ER stress results in misfolded protein aggregates, which are degraded through the process of autophagy or lead to cell death through activation of caspases. The regulation of crosstalk of autophagy and cell death during ER stress is emerging. Ubiquitination plays regulatory role in crosstalk of autophagy and cell death. In the current study, we describe the role of TRIM13, RING E3 ubiquitin ligase, in regulation of ER stress induced cell death. The expression of TRIM13 sensitizes cells to ER stress induced death. TRIM13 induced autophagy is essential for ER stress induced caspase activation and cell death. TRIM13 induces K63 linked poly-ubiquitination of caspase-8, which results in its stabilization and activation during ER stress. TRIM13 regulates translocation of caspase-8 to autophagosome and its fusion with lysosome during ER stress. This study first time demonstrated the role of TRIM13 as novel regulator of caspase-8 activation and cell death during ER stress.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fagossomos
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Proteínas Supressoras de Tumor
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Proteínas de Ligação a DNA
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Caspase 8
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Ubiquitinação
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Estresse do Retículo Endoplasmático
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article