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Involvement of MINK, a Ste20 Family Kinase, in Ras Oncogene-Induced Growth Arrest in Human Ovarian Surface Epithelial Cells
Open accessAbstract
The ability of activated Ras to induce growth arrest of human ovarian surface epithelial (HOSE) cells via induction of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) has been used to screen for Ras pathway signaling components using a library of RNA interference (RNAi) vectors targeting the kinome. Two known Ras-regulated kinases were identified, phosphoinositide 3-kinase p110alpha and ribosomal protein S6 kinase p70(S6K1), plus the MAP kinase kinase kinase kinase MINK, which had not previously been implicated in Ras signaling. MINK is activated after Ras induction via a mechanism involving reactive oxygen species and mediates stimulation of the stress-activated protein kinase p38 MAPK downstream of the Raf/ERK pathway. p38 MAPK activation is essential for Ras-induced p21(WAF1/CIP1) upregulation and cell cycle arrest. MINK is thus a distal target of Ras signaling in the induction of a growth-arrested, senescent-like phenotype that may act to oppose oncogenic transformation in HOSE cells.
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“Ras-induced senescence can be inhibited by using antioxidants or growing cells in low-oxygen conditions (8, 25, 33, 51).”
From Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence (2009) · cites this paper as [33]
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Metadata
- Authors
- Nicke, B., Bastien, J., Khanna, S. J., Warne, P. H., Cowling, V., Cook, S. J., Peters, G., Delpuech, O., Schulze, A., Berns, K., Mullenders, J., Beijersbergen, R. L., Bernards, R., Ganesan, T. S., Downward, J., & Hancock, D. C.
- Affiliations
- Cancer Research UK (GB)
- Babraham Institute (GB)
- The Netherlands Cancer Institute (NL)
- Corresponding author
- Downward, Julian
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 20
- Issue
- 5
- Pages
- 673-685
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2067838259
- Cited by
- 108
- References
- 47
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 4 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 1 · 2015: 4 · 2014: 7 · 2013: 4 · 2012: 6
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Cancer Research UK
- KWF Kankerbestrijding
- Biotechnology and Biological Sciences Research Council (BBS/E/B/0000C199, BBS/E/B/0000H457)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- mink, oncogenic Ras, ovarian surface epithelial cells, p21, growth arrest, p38 MAPK, RAF/ERK pathway, reactive oxygen species, senescence, oncogenic transformation, S6K1, cell cycle arrest
- MeSH terms
- Cell Cycle, Cell Transformation, Neoplastic, Epithelial Cells, Female, Humans, Ovarian Neoplasms, Phenotype, Signal Transduction, Proto-Oncogene Proteins p21(ras), Protein Serine-Threonine Kinases, Reactive Oxygen Species, MAP Kinase Kinase Kinases, Saccharomyces cerevisiae Proteins, RNA Interference, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21
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