Cited by 825Telomeres, Telomerase, and SenescenceCancer-related Molecular PathwaysGenetics, Aging, and Longevity in Model Organisms

Cellular senescence and tumor suppressor gene p16

Open access
Rayess, Hani, Wang, Marilene B., Srivatsan, Eri S.·2012·International Journal of Cancer

Abstract

Cellular senescence is an irreversible arrest of cell growth. Biochemical and morphological changes occur during cellular senescence, including the formation of a unique cellular morphology such as flattened cytoplasm. Function of mitochondria, endoplasmic reticulum and lysosomes are affected resulting in the inhibition of lysosomal and proteosomal pathways. Cellular senescence can be triggered by a number of factors including, aging, DNA damage, oncogene activation and oxidative stress. While the molecular mechanism of senescence involves p16 and p53 tumor suppressor genes and telomere shortening, this review is focused on the mechanism of p16 control. The p16‐mediated senescence acts through the retinoblastoma (Rb) pathway inhibiting the action of the cyclin dependant kinases leading to G1 cell cycle arrest. Rb is maintained in a hypophosphorylated state resulting in the inhibition of transcription factor E2F1. Regulation of p16 expression is complex and involves epigenetic control and multiple transcription factors. PRC1 (Pombe repressor complex (1) and PRC2 (Pombe repressor complex (2) proteins and histone deacetylases play an important role in the promoter hypermethylation for suppressing p16 expression. While transcription factors YY1 and Id1 suppress p16 expression, transcription factors CTCF, Sp1 and Ets family members activate p16 transcription. Senescence occurs with the inactivation of suppressor elements leading to the enhanced expression of p16.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/ijc.27316

Cites

124 of 124 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Both pathways exhibit substantial interconnections and crosstalk.

    “Furthermore, these pathways exhibit substantial interconnections and crosstalk (Rayess et al, 2012).”
  • Hypermethylation of the p16 gene promoter, which can lead to p16 inactivation, is often detected in many types of human cancers.

    “On the other hand, hypermethylation of the p16 gene promoter, which can lead to p16 inactivation, is often detected in many types of human cancers, suggesting the overcome of cellular senescence [21].”
  • After DDR activation, the p53/p21 pathway deactivates the cyclin E-CDK2 complex responsible for pRB phosphorylation, while the p16/pRB pathway inhibits pRB phosphorylation by deactivation of kinase CDK4/6.

    “After DDR activation, the p53/p21 pathway deactivates the cyclin E-CDK2 complex responsible for pRB phosphorylation [242], while the p16/pRB pathway inhibits pRB phosphorylation by deactivation of kinase CDK4/6 [239].”

    From Redox control of senescence and age-related disease. (2017) · cites this paper as [239]

  • Preventing pRB phosphorylation allows pRB to retain association with transcription factor E2F1, preventing expression of E2F1 target genes necessary for cell transition from G1 to S phase.

    “Preventing pRB phosphorylation allows pRB to retain its association with the transcription factor E2F1, preventing the expression of E2F1 target genes that are necessary for the cell transition from G1 to the S phase [239].”

    From Redox control of senescence and age-related disease. (2017) · cites this paper as [239]

  • The senescence phenotype is mediated through pathways activating p16INK4a/Rb and/or p53/p21, depending on inducer and cell type.

    “These inducers ultimately mediate the cellular senescence phenotype through mechanisms that converge on pathways that activate p16INK4a/Rb and/or p53/p21, depending on the inducer and cell type [20].”

    From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [20]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 3

  1. [55]Bannister AJ Zegerman P Partridge JF Miska EA Thomas JO Allshire RC Kouzarides T Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain Nature 2001 410 120 24 11242054
  2. [58]Dietrich N Bracken AP Trinh E Schjerling CK Koseki H Rappsilber J Helin K Hansen KH Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus Embo J 2007 26 1637 48 17332741 PMC1829390
  3. [79]Gil J Peters G Regulation of the INK4b-ARFINK4a tumor suppressor locus: All for one or one for all Nat Rev 2006 7 667 77 16921403

Cited by

Sorted by citations

Authors
Rayess, H., Wang, M. B., & Srivatsan, E. S.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Srivatsan, Eri S.
Venue
International Journal of Cancer
Publisher
Wiley
Published
2011-12-05
Volume
130
Issue
8
Pages
1715-1725
ISSN
  • 0020-7136 (ISSN-L)
  • 1097-0215
OpenAlex
W1996113298
Cited by
825
References
124
Citations by year
2026: 62 · 2025: 79 · 2024: 92 · 2023: 96 · 2022: 78 · 2021: 69 · 2020: 47 · 2019: 48 · 2018: 41 · 2017: 48 · 2016: 39 · 2015: 41 · 2014: 43 · 2013: 31 · 2012: 11
FWCI
2.91
Type
journal article
Language
en
Open access
Locations
  • International Journal of Cancer (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r21ca116826-02, R21 CA116826-01)
  • VA Greater Los Angeles Healthcare System
  • National Cancer Institute (R21 CA116826-01, R21 CA116826)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
cellular senescence, p16, tumor suppressor, retinoblastoma pathway, G1 cell cycle arrest, p53, telomere shortening, epigenetic regulation, promoter hypermethylation, histone deacetylase, transcription factors, DNA damage, oxidative stress, oncogene activation, aging
MeSH terms
Antineoplastic Agents, Humans, Neoplasms, Gene Expression, Tumor Suppressor Protein p53, Retinoblastoma Protein, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Cell Cycle Checkpoints, Telomere Shortening

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 ›

Are you an author, or do you see a problem with this page? Request a review