Evidence map›Paper›PMID 22558186›Full record

ArticlePloS one2012

CDK2 and PKA mediated-sequential phosphorylation is critical for p19INK4d function in the DNA damage response.

Mariela C Marazita, M Florencia Ogara, Silvina V Sonzogni, Marcelo Martí, Nelson J Dusetti, Omar P Pignataro, Eduardo T Cánepa

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

14 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Phosphoregulation of RAD51AP1 function in homology-directed repair.bioRxiv : the preprint server for biology · 2025
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Phosphorylation-induced unfolding regulates p19Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  8. Article
  9. Article
  10. Article
  11. Role of p19ink4d in the pathogenesis of hearing loss.International journal of clinical and experimental pathology · 2015
    Article
  12. Article
  13. Article
  14. Article
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

7 authors at 4 institutions in 2 countries.

Mariela C MarazitaLaboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
M Florencia Ogara
Silvina V Sonzogni
Marcelo Martí
Nelson J Dusetti
Omar P Pignataro
Eduardo T Cánepa
University of Buenos Aires · ARConsejo Nacional de Investigaciones Científicas y Técnicas · ARFundación Ciencias Exactas y Naturales · ARInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA damage triggers a phosphorylation-based signaling cascade known as the DNA damage response. p19INK4d, a member of the INK4 family of CDK4/6 inhibitors, has been reported to participate in the DNA damage response promoting DNA repair and cell survival. Here, we provide mechanistic insight into the activation mechanism of p19INK4d linked to the response to DNA damage. Results showed that p19INK4d becomes phosphorylated following UV radiation, β-amyloid peptide and cisplatin treatments. ATM-Chk2/ATR-Chk1 signaling pathways were found to be differentially involved in p19INK4d phosphorylation depending on the type of DNA damage. Two sequential phosphorylation events at serine 76 and threonine 141 were identified using p19INK4d single-point mutants in metabolic labeling assays with (32)P-orthophosphate. CDK2 and PKA were found to participate in p19INK4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19INK4d induced by DNA damage was shown to be dependent on serine 76 phosphorylation. Most importantly, both phosphorylation sites were found to be crucial for p19INK4d function in DNA repair and cell survival. In contrast, serine 76 and threonine 141 were dispensable for CDK4/6 inhibition highlighting the independence of p19INK4d functions, in agreement with our previous findings. These results constitute the first description of the activation mechanism of p19INK4d in response to genotoxic stress and demonstrate the functional relevance of this activation following DNA damage.

Indexed as

Amyloid beta-PeptidesCell CycleCell LineCell SurvivalCisplatinCyclic AMP-Dependent Protein KinasesCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p19DNADNA DamageDNA RepairGene Expression RegulationHEK293 CellsHumansMutationPhosphorylationAmyloid beta-PeptidesCDK2 protein, humanCisplatinCyclic AMP-Dependent Protein KinasesCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p19DNA

Identifiers

PMID22558186
PMCPMC3338453
OpenAlexW2042120994

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.