PreprintCited by 1,245Cancer-related Molecular PathwaysTelomeres, Telomerase, and SenescenceCell death mechanisms and regulation

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Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization

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Zindy, Frederique, Eischen, Christine M., Randle, David H., Kamijo, Takehiko, Cleveland, John L., Sherr, Charles J., Roussel, Martine F.·1998·Genes & Development

DOI 10.1101/gad.12.15.2424PMC PMC317045

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Abstract

Establishment of primary mouse embryo fibroblasts (MEFs) as continuously growing cell lines is normally accompanied by loss of the p53 or p19(ARF) tumor suppressors, which act in a common biochemical pathway. myc rapidly activates ARF and p53 gene expression in primary MEFs and triggers replicative crisis by inducing apoptosis. MEFs that survive myc overexpression sustain p53 mutation or ARF loss during the process of establishment and become immortal. MEFs lacking ARF or p53 exhibit an attenuated apoptotic response to myc ab initio and rapidly give rise to cell lines that proliferate in chemically defined medium lacking serum. Therefore, ARF regulates a p53-dependent checkpoint that safeguards cells against hyperproliferative, oncogenic signals.

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Authors: Zindy, F., Eischen, C. M., Randle, D. H., Kamijo, T., Cleveland, J. L., Sherr, C. J., & Roussel, M. F.
Affiliations: St. Jude Children's Research Hospital (US)
ORCID: Eischen, Christine M.
Kamijo, Takehiko
Cleveland, John L.
Sherr, Charles J.
Roussel, Martine F.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 1998-08-01
Volume: 12
Issue: 15
Pages: 2424-2433
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.12.15.2424
PMC: PMC317045
OpenAlex: W2046958356
Cited by: 1,245
References: 60
Citations by year: 2026: 6 · 2025: 15 · 2024: 14 · 2023: 32 · 2022: 10 · 2021: 27 · 2020: 15 · 2019: 22 · 2018: 15 · 2017: 23 · 2016: 28 · 2015: 19 · 2014: 43 · 2013: 45 · 2012: 46
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: St. Jude Children's Research Hospital (CA21765)
American Lebanese Syrian Associated Charities (CA 21765)
National Institutes of Health (5r01ca056819-08, CA21765))
National Cancer Institute (CA-71907, CA56819, P30CA021765, P01CA071907)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 44158, R01DK044158)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: MYC signaling, ARF tumor suppressor, p53, apoptosis, cell immortalization, p19ARF, TP53 mutation, oncogenic transformation
MeSH terms: Animals, Cell Division, Cell Line, Humans, Models, Biological, Mutation, Proteins, Signal Transduction, Gene Expression, Genes, Tumor Suppressor, Genes, p53, Genes, myc, Apoptosis, Gene Deletion, Tumor Suppressor Protein p14ARF, Mice

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Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization

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