Cited by 282Protein Kinase Regulation and GTPase SignalingMelanoma and MAPK PathwaysProtein Tyrosine Phosphatases

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Cellular Transformation and Malignancy Induced by ras Require c-jun

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Johnson, Randall, Spiegelman, Bruce, Hanahan, Douglas, Wisdom, Ron·1996·Molecular and Cellular Biology

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Abstract

ras is an important oncogene in experimental animals and humans. In addition, activated ras proteins are potent inducers of the transcription factor AP-1, which is composed of heterodimeric complexes of Fos and Jun proteins. Together with the fact that deregulated expression of some AP-1 proteins can cause neoplastic transformation, this finding suggests that AP-1 may function as a critical ras effector. We have tested this hypothesis directly by analyzing the response to activated ras in cells that harbor a null mutation in the c-jun gene. The transcriptional response of AP-1-responsive genes to activated ras is severely impaired in c-jun null fibroblasts. Compared with wild-type cells, the c-jun null cells lack many characteristics of ras transformation, including loss of contact inhibition, anchorage independence, and tumorigenicity in nude mice; these properties are restored by forced expression of c-jun. Rare tumorigenic variants of ras-expressing c-jun null fibroblasts do arise. Analysis of these variants reveals a consistent restoration of AP-1 activity. The results provide genetic evidence that c-jun is a crucial effector for transformation by activated ras proteins.

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Authors: Johnson, R., Spiegelman, B., Hanahan, D., & Wisdom, R.
Affiliations: University of California, San Francisco (US)
Harvard University (US)
Vanderbilt University (US)
ORCID: Johnson, Randall
Spiegelman, Bruce
Hanahan, Douglas
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 1996-08
Volume: 16
Issue: 8
Pages: 4504-4511
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.16.8.4504
PMC: PMC231449
OpenAlex: W1895834181
Cited by: 282
References: 61
Citations by year: 2026: 1 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 1 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 6 · 2015: 7 · 2014: 4 · 2013: 8 · 2012: 2
FWCI: 6.82
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Cancer Society
National Institutes of Health
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 › Melanoma and MAPK Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords: c-Jun, oncogenic Ras, AP-1 transcription factor, Fos-Jun heterodimer, oncogenic transformation, anchorage-independent growth, tumorigenicity, Ras effectors
MeSH terms: Animals, Base Sequence, Cell Cycle, Cell Transformation, Neoplastic, Cells, Cultured, Molecular Sequence Data, Oligodeoxyribonucleotides, Genes, ras, Proto-Oncogene Proteins p21(ras), Proto-Oncogene Proteins c-jun, Genes, jun, Mice, Knockout, Mice

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Cellular Transformation and Malignancy Induced by ras Require c-jun

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