Cited by 844Cancer-related Molecular PathwaysTelomeres, Telomerase, and SenescenceChromatin Remodeling and Cancer

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Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all

Gil, Jesús, Peters, Gordon·2006·Nature Reviews Molecular Cell Biology

DOI 10.1038/nrm1987

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Abstract

The INK4b-ARF-INK4a locus encodes two members of the INK4 family of cyclin-dependent kinase inhibitors, p15(INK4b) and p16(INK4a), and a completely unrelated protein, known as ARF. All three products participate in major tumour suppressor networks that are disabled in human cancer and influence key physiological processes such as replicative senescence, apoptosis and stem-cell self-renewal. Transcription from the locus is therefore kept under strict control. Mounting evidence suggests that although the individual genes can respond independently to positive and negative signals in different contexts, the entire locus might be coordinately suppressed by a cis-acting regulatory domain or by the action of Polycomb group repressor complexes.

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Authors: Gil, J., & Peters, G.
Affiliations: Imperial College London (GB)
Cancer Research UK (GB)
Corresponding author: Peters, Gordon
ORCID: Gil, Jesús
Venue: Nature Reviews Molecular Cell Biology
Publisher: Springer Science and Business Media LLC
Published: 2006-09-01
Volume: 7
Issue: 9
Pages: 667-677
ISSN: 1471-0072 (ISSN-L)
1471-0080
DOI: 10.1038/nrm1987
OpenAlex: W2056495027
Cited by: 843
References: 153
Citations by year: 2026: 13 · 2025: 23 · 2024: 24 · 2023: 35 · 2022: 38 · 2021: 30 · 2020: 33 · 2019: 32 · 2018: 35 · 2017: 48 · 2016: 48 · 2015: 53 · 2014: 48 · 2013: 56 · 2012: 58
FWCI: 4.03
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Reviews Molecular Cell Biology (publishedVersion)
PubMed (publishedVersion)
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 › Chromatin Remodeling and Cancer
Keywords: tumor suppressor, CDKN2B, p16INK4a, Arf proteins, cyclin-dependent kinase inhibitors, cis-regulatory elements, replicative senescence, apoptosis, stem cell self-renewal, transcriptional regulation, cancer
MeSH terms: Animals, Gene Expression Regulation, Humans, Repressor Proteins, Stem Cells, Signal Transduction, Cellular Senescence, Apoptosis, Cyclin-Dependent Kinase Inhibitor p16, ADP-Ribosylation Factors, Quantitative Trait Loci, Cyclin-Dependent Kinase Inhibitor p15, Polycomb-Group Proteins

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Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all

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