ArticleProceedings of the National Academy of Sciences of the United States of America2012
Site-specific ubiquitination is required for relieving the transcription factor Miz1-mediated suppression on TNF-α-induced JNK activation and inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 33 citations in OpenAlex.
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- Understanding the Underlying Molecular Mechanisms of Meiotic Arrest during In Vitro Spermatogenesis in Rat Prepubertal Testicular Tissue.International journal of molecular sciences · 2022Article
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- Role of RING-Type E3 Ubiquitin Ligases in Inflammatory Signalling and Inflammatory Bowel Disease.Mediators of inflammation · 2020Review
- Ghrelin protects against contact dermatitis and psoriasiform skin inflammation by antagonizing TNF-α/NF-κB signaling pathways.Scientific reports · 2019Article
- Ubiquitination by HUWE1 in tumorigenesis and beyond.Journal of biomedical science · 2018Review
- The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E-cadherin-mediated adherens junctions.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Anticancer effect of fufang yiliu yin on human hepatocellular carcinoma SMMC-7721 cells.American journal of translational research · 2018Article
- Ubc13: the Lys63 ubiquitin chain building machine.Oncotarget · 2016Review
- Syk-mediated tyrosine phosphorylation of mule promotes TNF-induced JNK activation and cell death.Oncogene · 2016Article
- Decreased MIZ1 Expression in Severe Experimental Acute Pancreatitis: A Rat Study.Digestive diseases and sciences · 2016Article
- The kinase Jnk2 promotes stress-induced mitophagy by targeting the small mitochondrial form of the tumor suppressor ARF for degradation.Nature immunology · 2015Article
- Tumor necrosis factor receptor-associated factor 2 mediates mitochondrial autophagy.Circulation. Heart failure · 2015Article
- Miz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.PloS one · 2014Article
- The role of MIZ-1 in MYC-dependent tumorigenesis.Cold Spring Harbor perspectives in medicine · 2013Review
- Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1-mediated down-regulation of p21 and p15.Genes & development · 2013Article
- Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ.Nature immunology · 2013Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The transcription factor zinc-finger protein Miz1 represses TNF-α-induced JNK activation and the repression is relieved upon TNF-α stimulation. However, the underlying mechanism is incompletely understood. Here we report that Miz1 interferes with the ubiquitin conjugating enzyme (E2) Ubc13 for binding to the RING domain of TNF-receptor associated factor 2 (TRAF2), thereby inhibiting the ubiquitin ligase (E3) activity of TRAF2 and suppressing TNF-α-induced JNK activation. Upon TNF-α stimulation, Miz1 rapidly undergoes K48-linked polyubiquitination at Lys388 and Lys472 residues and subsequent proteasomal degradation in a TRAF2-dependent manner. Replacement of Lysine 388 and Lysine 472 by arginines generates a nondegradable Miz1 mutant, which significantly suppresses TNF-α-induced JNK1 activation and inflammation. Thus, our results reveal a molecular mechanism by which the repression of TNF-α-induced JNK activation by Miz1 is de-repressed by its own site-specific ubiquitination and degradation, which may account for the temporal control of TNF-α-JNK signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.