Arrest of G 1 -S Progression by the p53-Inducible Gene PC3 Is Rb Dependent and Relies on the Inhibition of Cyclin D1 Transcription
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The p53-inducible gene PC3 (TIS21, BTG2) is endowed with antiproliferative activity. Here we report that expression of PC3 in cycling cells induced accumulation of hypophosphorylated, growth-inhibitory forms of pRb and led to G(1) arrest. This latter was not observed in cells with genetic disruption of the Rb gene, indicating that the PC3-mediated G(1) arrest was Rb dependent. Furthermore, (i) the arrest of G(1)-S transition exerted by PC3 was completely rescued by coexpression of cyclin D1 but not by that of cyclin A or E; (ii) expression of PC3 caused a significant down-regulation of cyclin D1 protein levels, also in Rb-defective cells, accompanied by inhibition of CDK4 activity in vivo; and (iii) the removal from the PC3 molecule of residues 50 to 68, a conserved domain of the PC3/BTG/Tob gene family, which we term GR, led to a loss of the inhibition of proliferation as well as of the down-regulation of cyclin D1 levels. These data point to cyclin D1 down-regulation as the main factor responsible for the growth inhibition by PC3. Such an effect was associated with a decrease of cyclin D1 transcript and of cyclin D1 promoter activity, whereas no effect of PC3 was observed on cyclin D1 protein stability. Taken together, these findings indicate that PC3 impairs G(1)-S transition by inhibiting pRb function in consequence of a reduction of cyclin D1 levels and that PC3 acts, either directly or indirectly, as a transcriptional regulator of cyclin D1.
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BTG2 can induce G1/S cell cycle arrest.
“The p53 target genes BTG236, 154, 155 and GADD45A13, 156 can also induce G1/S and G2/M cell cycle arrest, respectively.”
From Census and evaluation of p53 target genes (2017) · cites this paper as [154]
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Self-citation
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Census and evaluation of p53 target genes
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- Authors
- Guardavaccaro, D., Corrente, G., Covone, F., Micheli, L., D'Agnano, I., Starace, G., Caruso, M., & Tirone, F.
- Affiliations
- Institute of Neurobiology and Molecular Medicine (IT)
- Istituto di Tecnologie Biomediche
- Istituto di Medicina Sperimentale
- National Research Council (IT)
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-03
- Volume
- 20
- Issue
- 5
- Pages
- 1797-1815
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC85361
- OpenAlex
- W1980093005
- Cited by
- 230
- References
- 124
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 1 · 2020: 1 · 2019: 6 · 2018: 10 · 2017: 3 · 2016: 11 · 2015: 12 · 2014: 7 · 2013: 7 · 2012: 15
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Signaling Pathways in Disease
- Keywords
- PC-3 cells, BTG2, G1/S transition, cell cycle arrest, retinoblastoma protein, cyclin D1, CDK4, transcriptional regulation, antiproliferative activity, growth inhibition
- MeSH terms
- Animals, Cell Cycle, Gene Expression Regulation, Transcription, Genetic, Tumor Suppressor Protein p53, Retinoblastoma Protein, G1 Phase, S Phase, Aspartic Acid Endopeptidases, 3T3 Cells, Cyclin D1, Proprotein Convertases, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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