Evidence map›Paper›PMID 22496453›Full record

ArticleThe Journal of biological chemistry2012

Roles of Kruppel-associated Box (KRAB)-associated Co-repressor KAP1 Ser-473 Phosphorylation in DNA Damage Response.

Chen Hu, Shengping Zhang, Xuan Gao, Xiaojing Gao, Xiaohong Xu, Ya Lv, Yan Zhang, Zhenhong Zhu, Changqing Zhang, Qiao Li and 5 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% 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

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.

  1. Pooled it
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  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
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  11. Article
  12. Article
  13. KAP1 in antiviral immunity: dual roles in viral silencing and immune regulation.Frontiers in cellular and infection microbiology · 2025
    Review
  14. Multifaceted role ofMedComm · 2024
    Review
  15. Review
  16. TRIM28 in cancer and cancer therapy.Frontiers in genetics · 2024
    Review
  17. Article
  18. Article
  19. Article
  20. 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

15 authors at 4 institutions in 2 countries.

Chen HuShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and College of Life Science and.
Shengping Zhang
Xuan Gao
Xiaojing Gao
Xiaohong Xu
Ya Lv
Yan Zhang
Zhenhong Zhu
Changqing Zhang
Qiao Li
Jiemin Wong
Yongping Cui
Wen Zhang
Lin Ma
Chuangui Wang
East China Normal University · CNShanghai Jiao Tong University · CNShanxi Medical University · CNUniversity of Ottawa · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Kruppel-associated box (KRAB)-associated co-repressor KAP1 is an essential nuclear co-repressor for the KRAB zinc finger protein superfamily of transcriptional factors. Ataxia telangiectasia mutated (ATM)-Chk2 and ATM- and Rad3-related (ATR)-Chk1 are two primary kinase signaling cascades activated in response to DNA damage. A growing body of evidence suggests that ATM and ATR phosphorylate KAP1 at Ser-824 in response to DNA damage and regulate KAP1-dependent chromatin condensation, DNA repair, and gene expression. Here, we show that, depending on the type of DNA damage that occurs, KAP1 Ser-473 can be phosphorylated by ATM-Chk2 or ATR-Chk1 kinases. Phosphorylation of KAP1 at Ser-473 attenuated its binding to the heterochromatin protein 1 family proteins and inhibited its transcriptional repression of KRAB-zinc finger protein (KRAB-ZFP) target genes. Moreover, KAP1 Ser-473 phosphorylation induced by DNA damage stimulated KAP1-E2F1 binding. Overexpression of heterochromatin protein 1 significantly inhibited E2F1-KAP1 binding. Elimination of KAP1 Ser-473 phosphorylation increased E2F1-targeted proapoptotic gene expression and E2F1-induced apoptosis in response to DNA damage. Furthermore, loss of phosphorylation of KAP1 Ser-473 led to less BRCA1 focus formation and slower kinetics of loss of γH2AX foci after DNA damage. KAP1 Ser-473 phosphorylation was required for efficient DNA repair and cell survival in response to DNA damage. Our studies reveal novel functions of KAP1 Ser-473 phosphorylation under stress.

Indexed as

Chromatin Assembly and DisassemblyDNA DamageApoptosisAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCheckpoint Kinase 1Checkpoint Kinase 2DNA-Binding ProteinsE2F1 Transcription FactorHEK293 CellsHeLa CellsHumansPhosphorylationProtein KinasesProtein Serine-Threonine KinasesRepressor ProteinsAtaxia Telangiectasia Mutated ProteinsATM protein, humanATR protein, humanCell Cycle ProteinsCheckpoint Kinase 1Checkpoint Kinase 2CHEK1 protein, humanCHEK2 protein, humanDNA-Binding ProteinsE2F1 protein, humanE2F1 Transcription FactorProtein KinasesProtein Serine-Threonine KinasesRepressor ProteinsSerineTRIM28 protein, humanTripartite Motif-Containing Protein 28Tumor Suppressor Proteins

Identifiers

PMID22496453
PMCPMC3365928
OpenAlexW2010276959

What OpenQuestion holds

Textmetadata
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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.