title: TRIM13 regulates caspase-8 ubiquitination, translocation to autophagosomes and activation during ER stress induced cell death.
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.
authors.affiliation: Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, Gujarat, India.
authors.forename: Dhanendra
authors.initials: D
authors.lastname: Tomar
authors.affiliation: Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, Gujarat, India.
authors.forename: Paresh
authors.initials: P
authors.lastname: Prajapati
authors.affiliation: Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, Gujarat, India.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Sripada
authors.affiliation: Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, Gujarat, India.
authors.forename: Kritarth
authors.initials: K
authors.lastname: Singh
authors.affiliation: Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, Gujarat, India.
authors.forename: Rochika
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, Gujarat, India.
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, Gujarat, India. Electronic address: rsingh@iiar.res.in.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Singh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D053181:Caspase 8 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D061986:MCF-7 Cells; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D000071701:Regulatory Factor X Transcription Factors; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology; D054875:Ubiquitination / Q000187:drug effects; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C112217:TRIM13 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014415:Tunicamycin; D053181:Caspase 8
keywords: Autophagy; Caspase-8; Cell death; Endoplasmic reticulum stress; TRIM13; Ubiquitin ligase