ArticleThe Journal of biological chemistry2013
Lysine 63-linked ubiquitination modulates mixed lineage kinase-3 interaction with JIP1 scaffold protein in cytokine-induced pancreatic β cell death.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- MARCH2-mediated Lys63-linked polyubiquitination promotes metastasis by modulating the catalytic activity of TGF-β type I receptor.Cell death & disease · 2025Article
- SPHK1 potentiates colorectal cancer progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination.Cancer gene therapy · 2024Article
- Mixed-lineage kinase 3 pharmacological inhibition attenuates murine nonalcoholic steatohepatitis.JCI insight · 2017Article
- TNFα-induced DLK activation contributes to apoptosis in the beta-cell line HIT.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- Mixed lineage kinase 3 mediates release of C-X-C motif ligand 10-bearing chemotactic extracellular vesicles from lipotoxic hepatocytes.Hepatology (Baltimore, Md.) · 2016Article
- Protein-Binding Function of RNA-Dependent Protein Kinase Promotes Proliferation through TRAF2/RIP1/NF-κB/c-Myc Pathway in Pancreatic β cells.Molecular medicine (Cambridge, Mass.) · 2015Article
- Ubiquitin-specific protease 14 regulates c-Jun N-terminal kinase signaling at the neuromuscular junction.Molecular neurodegeneration · 2015Article
- Distinct effects of ubiquitin overexpression on NMJ structure and motor performance in mice expressing catalytically inactive USP14.Frontiers in molecular neuroscience · 2015Article
- Loss of TRB3 alters dynamics of MLK3-JNK signaling and inhibits cytokine-activated pancreatic beta cell death.The Journal of biological chemistry · 2014Article
- The E3 ligase CHIP mediates ubiquitination and degradation of mixed-lineage kinase 3.Molecular and cellular biology · 2014Article
- TNF and MAP kinase signalling pathways.Seminars in immunology · 2014Review
- Hepatitis C virus NS5A inhibits mixed lineage kinase 3 to block apoptosis.The Journal of biological chemistry · 2013Article
- mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6.Nature cell biology · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The mixed lineage kinase MLK3 plays a crucial role in compromising mitochondrial integrity and functions as a proapoptotic competence factor in the early stages of cytokine-induced pancreatic β cell death. In an effort to identify mechanisms that regulate MLK3 activity in β cells, we discovered that IL-1β stimulates Lys-63-linked ubiquitination of MLK3 via a conserved, TRAF6-binding peptapeptide motif in the catalytic domain of the kinase. TRAF6-mediated ubiquitination was required for dissociation of inactive monomeric MLK3 from the scaffold protein IB1/JIP1, facilitating the subsequent dimerization, autophosphorylation, and catalytic activation of MLK3. Inability to ubiquitinate MLK3, or the presence of A20, an upstream Lys-63-linked deubiquitinase, strongly curtailed the ability of MLK3 to affect the proapoptotic translocation of BAX in cytokine-stimulated pancreatic β cells, an early step in the progression toward β cell death. These studies suggest a novel mechanism for MLK3 activation and provide new clues for therapeutic intervention in promoting β cell survival.
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