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Cited by 34Cancer-related Molecular PathwaysProtein Kinase Regulation and GTPase SignalingGenomics and Chromatin Dynamics

E2F and Ras Synergize in Transcriptionally Activating p14ARFExpression

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Berkovich, Eli, Lamed, Yocheved, Ginsberg, Doron·2003·Cell Cycle
DOI 10.4161/cc.2.2.293
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Abstract

The INK4a/ARF locus, which is frequently inactivated in human tumors, encodes two distinct tumor suppressive proteins, ARF and p16INK4a. ARF stabilizes and activates p53 by negating the effects of mdm2 on p53. Furthermore, its function is not restricted to the p53 pathway and it also inhibits cell proliferation in cells lacking p53. Expression of ARF is up-regulated in response to a number of oncogenic stimuli including E2F1. We show here that while oncogenic Ras does not significantly affect p1(4AR)F expression in normal human cells it activates p1(4AR)F in cells containing deregulated E2F. Moreover, oncogenic Ras and E2F1 synergize in activating p1(4AR)F expression. Activation of p1(4AR)F promoter by E2F1 persists in the absence of the consensus E2F-binding sites in this promoter, indicating that this activation also occurs through non- canonical binding sites. The activation by oncogenic Ras requires both E2F and Sp-1 activity, demonstrating the complex regulation of p14(ARF) in response to oncogenic stimuli.

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  • Delayed ARF expression increase probably reflects the complex organization of responsive elements within the ARF promoter.

    “The delayed ARF expression increase probably reflects the complex organization of the responsive elements within the ARF promoter [130,131,132].”

    From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [132]

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Authors
Berkovich, E., Lamed, Y., & Ginsberg, D.
Affiliations
Weizmann Institute of Science (IL)
ORCID
Ginsberg, Doron
Venue
Cell Cycle
Publisher
Informa UK Limited
Published
2003-03-07
Volume
2
Issue
2
Pages
127-134
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
DOI
10.4161/cc.2.2.293
OpenAlex
W1980021034
Cited by
33
References
0
Citations by year
2024: 1 · 2021: 1 · 2019: 3 · 2016: 2 · 2014: 2 · 2013: 3 · 2012: 1
FWCI
1.80
Type
journal article
Language
en
Open access
Locations
  • Cell Cycle (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Israel Cancer Research Fund
  • Minerva Foundation
  • Israel Cancer Association
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
p14ARF, E2F1, oncogenic Ras, transcriptional activation, INK4a/ARF locus, p53, Sp1, tumor suppressor, gene expression regulation
MeSH terms
Animals, Cell Line, DNA-Binding Proteins, Genetic Vectors, Humans, Promoter Regions, Genetic, Genes, ras, Transcription Factors, Transcriptional Activation, Up-Regulation, Sp1 Transcription Factor, Cell Cycle Proteins, Tumor Suppressor Protein p14ARF, E2F Transcription Factors, E2F1 Transcription Factor, Mice

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