ArticleMolecular and cellular biology2003
The COOH-terminal domain of wild-type Cot regulates its stability and kinase specific activity.
Article in Molecular and cellular biology, 2003. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 55 citations in OpenAlex.
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- Melanocytic tumors with MAP3K8 fusions: report of 33 cases with morphological-genetic correlations.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Identification of Targetable Recurrent MAP3K8 Rearrangements in Melanomas Lacking Known Driver Mutations.Molecular cancer research : MCR · 2019Article
- Clinical genome sequencing uncovers potentially targetable truncations and fusions of MAP3K8 in spitzoid and other melanomas.Nature medicine · 2019Article
- Tumor progression locus 2 (Tpl2) kinase as a novel therapeutic target for cancer: double-sided effects of Tpl2 on cancer.International journal of molecular sciences · 2015Review
- IκB kinase-induced interaction of TPL-2 kinase with 14-3-3 is essential for Toll-like receptor activation of ERK-1 and -2 MAP kinases.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Cot/tpl2 participates in the activation of macrophages by adiponectin.Journal of leukocyte biology · 2014Article
- Sterile inflammation in acetaminophen-induced liver injury is mediated by Cot/tpl2.The Journal of biological chemistry · 2013Article
- Cot/tpl2-MKK1/2-Erk1/2 controls mTORC1-mediated mRNA translation in Toll-like receptor-activated macrophages.Molecular biology of the cell · 2012Article
- Regulation and function of TPL-2, an IκB kinase-regulated MAP kinase kinase kinase.Cell research · 2011Review
- Cot/tpl2 (MAP3K8) mediates myeloperoxidase activity and hypernociception following peripheral inflammation.The Journal of biological chemistry · 2010Article
- Article
- Cytomegalovirus promoter up-regulation is the major cause of increased protein levels of unstable reporter proteins after treatment of living cells with proteasome inhibitors.The Journal of biological chemistry · 2009Article
- Phosphorylation of TPL-2 on serine 400 is essential for lipopolysaccharide activation of extracellular signal-regulated kinase in macrophages.Molecular and cellular biology · 2007Article
- Phosphorylation at Thr-290 regulates Tpl2 binding to NF-kappaB1/p105 and Tpl2 activation and degradation by lipopolysaccharide.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- Neoplasia-associated Chromosome Translocations Resulting in Gene Truncation.Cancer genomics & proteomicsReview
- Genetic Pathways in Peritoneal Mesothelioma Tumorigenesis.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cot, initially identified as an oncogene in a truncated form, is a mitogen-activated protein kinase kinase kinase implicated in cellular activation and proliferation. Here, we show that this truncation of Cot results in a 10-fold increase in its overall kinase activity through two different mechanisms. Truncated Cot protein exhibits a lower turnover rate (half-life, 95 min) than wild-type Cot (half-life, 35 min). The degradation of wild-type and truncated Cot can be specifically inhibited by proteasome inhibitors in situ. The 20S proteasome also degrades wild-type Cot more efficiently than the truncated protein. Furthermore, the amino acid 435 to 457 region within the wild-type Cot COOH-terminal domain confers instability when transferred to the yellow fluorescent protein and targets this fusion protein to degradation via the proteasome. On the other hand, the kinase specific activity of wild-type Cot is 3.8-fold lower than that of truncated Cot, and it appears that the last 43 amino acids of the wild-type Cot COOH-terminal domain are those responsible for this inhibition of kinase activity. In conclusion, these data demonstrate that the oncogenic activity of truncated Cot is the result of its prolonged half-life and its higher kinase specific activity with respect to wild-type Cot.
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Registered trials
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.