Evidence map›Paper›PMID 25394905›Full record

ArticleNature communications2014

Histone H3.3 and its proteolytically processed form drive a cellular senescence programme.

Luis F Duarte, Andrew R J Young, Zichen Wang, Hsan-Au Wu, Taniya Panda, Yan Kou, Avnish Kapoor, Dan Hasson, Nicholas R Mills, Avi Ma'ayan and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

102 citing papers in PubMed, 162 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Interrogating the regulatory epigenome of cellular senescence.Cellular and molecular life sciences : CMLS · 2025
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Histone Tail Cleavage as a Mechanism for Epigenetic Regulation.International journal of molecular sciences · 2024
    Review
  18. Article
  19. Review
  20. Review

42 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Luis F Duarte1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA [2] Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA [3] Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Andrew R J YoungCancer Research UK Cambridge Institute, University of Cambridge, The Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Zichen Wang1] Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA [2] Department of Pharmacology and Systems Therapeutics and Systems Biology Center New York (SBCNY), Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Hsan-Au Wu1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA [2] Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Taniya Panda1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA [2] Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Yan Kou1] Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA [2] Department of Pharmacology and Systems Therapeutics and Systems Biology Center New York (SBCNY), Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Avnish Kapoor1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA [2] Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Dan Hasson1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA [2] Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Nicholas R Mills1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA [2] Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Avi Ma'ayanDepartment of Pharmacology and Systems Therapeutics and Systems Biology Center New York (SBCNY), Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Masashi NaritaCancer Research UK Cambridge Institute, University of Cambridge, The Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Emily Bernstein1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA [2] Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Icahn School of Medicine at Mount Sinai · USUniversity of Cambridge · GB

Funding

Data Coordination and Integration Center for LINCS-BD2KU54HL127624 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MA'AYAN, AVI, SCHURER, STEPHAN C · 2014 to 2019
$23.5M
System Biology Center in New YorkP50GM071558 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ZAPH, SUSANA NEVES · 2007 to 2017
$22.8M
TRAINING PROGRAM IN CANCER THERAPYT32CA078207 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI James J Manfredi · 1999 to 2026
$11.6M
Deciphering the tumor suppressive functions of macroH2AR01CA154683 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BERNSTEIN, EMILY · 2011 to 2021
$3.9M
User Interface PortalU54CA189201 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DUDLEY, JOEL THOMAS, MA'AYAN, AVI · 2014 to 2017
$1.9M
Expression2Kinases: mRNA Profiling Linked to Multiple Upstream Regulatory LayersR01GM098316 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MA'AYAN, AVI · 2012 to 2015
$1.3M
Cancer Research UK 15890NCI NIH HHS NCI/NIH R01CA154683NCI NIH HHS R01 CA154683NCI NIH HHS T32 CA078207NCI NIH HHS T32CA078207NCI NIH HHS U54 CA189201NHLBI NIH HHS U54 HL127624NIGMS NIH HHS P50 GM071558NIGMS NIH HHS P50GM071558NIGMS NIH HHS R01 GM098316NIGMS NIH HHS R01GM098316
6 · The paper itself

Abstract

The process of cellular senescence generates a repressive chromatin environment, however, the role of histone variants and histone proteolytic cleavage in senescence remains unclear. Here, using models of oncogene-induced and replicative senescence, we report novel histone H3 tail cleavage events mediated by the protease Cathepsin L. We find that cleaved forms of H3 are nucleosomal and the histone variant H3.3 is the preferred cleaved form of H3. Ectopic expression of H3.3 and its cleavage product (H3.3cs1), which lacks the first 21 amino acids of the H3 tail, is sufficient to induce senescence. Further, H3.3cs1 chromatin incorporation is mediated by the HUCA histone chaperone complex. Genome-wide transcriptional profiling revealed that H3.3cs1 facilitates transcriptional silencing of cell cycle regulators including RB/E2F target genes, likely via the permanent removal of H3K4me3. Collectively, our study identifies histone H3.3 and its proteolytically processed forms as key regulators of cellular senescence.

Indexed as

Cathepsin LCell CycleCellular SenescenceChromatinE2F Transcription FactorsEctopic Gene ExpressionFibroblastsHistonesHumansMelanocytesNucleosomesProteolysisRepressor ProteinsCathepsin LChromatinCTSL protein, humanE2F Transcription FactorsHistonesNucleosomesRepressor Proteins

Identifiers

PMID25394905
PMCPMC4235654
OpenAlexW1982474866

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.