Cited by 108Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesMelanoma and MAPK Pathways

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Involvement of MINK, a Ste20 Family Kinase, in Ras Oncogene-Induced Growth Arrest in Human Ovarian Surface Epithelial Cells

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Nicke, Barbara, Bastien, Julie, Khanna, Sophia J., Warne, Patricia H., Cowling, Victoria, Cook, Simon J., Peters, Gordon, Delpuech, Oona, Schulze, Almut, Berns, Katrien, Mullenders, Jasper, Beijersbergen, Roderick L., Bernards, René, Ganesan, Trivadi S., Downward, Julian, Hancock, David C.·2005·Molecular Cell

DOI 10.1016/j.molcel.2005.10.038

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Abstract

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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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: Nicke, Barbara
Cowling, Victoria
Cook, Simon J.
Delpuech, Oona
Schulze, Almut
Berns, Katrien
Mullenders, Jasper
Beijersbergen, Roderick L.
Bernards, René
Ganesan, Trivadi S.
Downward, Julian
Hancock, David C.
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 2005-12
Volume: 20
Issue: 5
Pages: 673-685
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/j.molcel.2005.10.038
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2821 d)
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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Involvement of MINK, a Ste20 Family Kinase, in Ras Oncogene-Induced Growth Arrest in Human Ovarian Surface Epithelial Cells

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