The DOI matches its Crossref record; 46 of the 47 references it cites were found in a registry or an index.
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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Cites
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 4×
“It therefore appears that inducible expression of Ras leads to a growth arrest in this ovarian epithelial cell system by a mechanism that does not involve either p53 or p16, the two pathways most commonly associated with oncogene-induced growth arrest (Lloyd et al., 1997; Serrano et al., 1997; Sewing et al., 1997).”
BackgroundInfluentialTargeting RAS signalling pathways in cancer therapy
Downward, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc969 · Cited by 3,354
Self-citationSenescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
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“…the PI 3-kinase inhibitor LY294002 has previously been reported to block hydrogen peroxide-induced senescence in human diploid fibroblasts (Wang et al., 2004) and PTEN deletion has recently been associated with induction of p53-dependent senescence in mouse prostate glands (Chen et al., 2005).”
BackgroundCreation of human tumour cells with defined genetic elements
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Self-citationBRAFE600-associated senescence-like cell cycle arrest of human naevi
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Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
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Phosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954
Self-citationMitogenic Signaling Mediated by Oxidants in Ras-Transformed Fibroblasts
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Lowe, S. W., Cepero, E., & Evan, G. I. (2004) · Nature · doi:10.1038/nature03098 · Cited by 1,374
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Items 101–108 of 108
Wu, M.-Y., Luo, H., Chang, Y.-C., Yu, C., & Sung, W. (2024) · PLoS ONE · doi:10.1371/journal.pone.0303334
p38α and p38β regulate osmostress-induced apoptosis
Messaoud, N. B., & López, J. M. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.108061
Torshin, I. Y., Громова, О. А., Александрович, Р. М., & Николаевич, Г. А. (2026) · FARMAKOEKONOMIKA Modern Pharmacoeconomics and Pharmacoepidemiology · doi:10.17749/2070-4909/farmakoekonomika.2026.361
Nuclear Import of Smad: A Dissertation
Chen, X. (2011) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/qrcn-m077
The Senescent Cell Induced Bystander Effect
Wordsworth, J. (2014)
Bulavin, D. V. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00271-0
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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