ArticleMolecular and cellular biology2000
Multiple mitogen-activated protein kinase signaling pathways connect the cot oncoprotein to the c-jun promoter and to cellular transformation.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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79 citing papers in PubMed, 191 citations in OpenAlex.
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- IFN-γ-inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5.Science signaling · 2018Article
- Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy.Acta pharmaceutica Sinica. B · 2018Review
- C3G promotes a selective release of angiogenic factors from activated mouse platelets to regulate angiogenesis and tumor metastasis.Oncotarget · 2017Article
- Cot kinase plays a critical role in Helicobacter pylori-induced IL-8 expression.Journal of microbiology (Seoul, Korea) · 2017Article
- Deletion of tumor progression locus 2 attenuates alcohol-induced hepatic inflammation.Hepatobiliary surgery and nutrition · 2016Article
- Tumor cells with KRAS or BRAF mutations or ERK5/MAPK7 amplification are not addicted to ERK5 activity for cell proliferation.Cell cycle (Georgetown, Tex.) · 2016Article
- MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas.Nature communications · 2015Article
- MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road.Nature reviews. Cancer · 2015Review
- Extracellular signal-regulated kinase 5 promotes acute cellular and systemic inflammation.Science signaling · 2015Article
- The Potential of Vitamin D-Regulated Intracellular Signaling Pathways as Targets for Myeloid Leukemia Therapy.Journal of clinical medicine · 2015Review
- 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
- The interplay between cyclic AMP, MAPK, and NF-κB pathways in response to proinflammatory signals in microglia.BioMed research international · 2015Article
- RelB-induced expression of Cot, an MAP3K family member, rescues RANKL-induced osteoclastogenesis in alymphoplasia mice by promoting NF-κB2 processing by IKKα.The Journal of biological chemistry · 2014Article
- Mitogen-activated protein kinase-mediated licensing of interferon regulatory factor 3/7 reinforces the cell response to virus.The Journal of biological chemistry · 2014Article
- How MAP kinase modules function as robust, yet adaptable, circuits.Cell cycle (Georgetown, Tex.) · 2014Article
19 more citing papers are in PubMed but not listed here.
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3 authors at 1 institution in 1 country.
Funding
Abstract
The serine/threonine kinase Cot is a member of the mitogen-activated protein kinase (MAPK) kinase kinase family implicated in cellular transformation. Enhanced expression of this protein has been shown to activate both the MAPK and the c-Jun N-terminal kinase (JNK) pathways and to stimulate the nuclear factor of activated T cells and NF-kappaB-dependent transcription. However, the nature of the normal functions of the Cot protein and the molecular mechanisms responsible for its oncogenic potential are still largely unknown. Here, we show that overexpression of the cot proto-oncogene is sufficient to stimulate the expression of c-jun and that, in turn, the activity of c-Jun is required for Cot-induced transformation. These observations prompted us to explore the molecular events by which Cot regulates c-jun expression. We found that Cot potently stimulates the activity of the c-jun promoter utilizing JNK-dependent and -independent pathways, the latter involving two novel members of the MAPK family, p38gamma (ERK6) and ERK5. Molecularly, this activity was found to be dependent on the ability of Cot to activate, in vivo, members of each class of the MAPK kinase superfamily, including MEK, SEK, MKK6, and MEK5. Furthermore, the use of dominant interfering molecules revealed that Cot requires JNK, p38s, and ERK5 to stimulate the c-jun promoter fully and to induce neoplastic transformation. These findings indicate that Cot represents the first example of a serine/threonine kinase acting simultaneously on all known MAPK cascades. Moreover, these observations strongly suggest that the transforming ability of Cot results from the coordinated activation of these pathways, which ultimately converge on the regulation of the expression and activity of the product of the c-jun proto-oncogene.
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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.