Evidence map›Paper›PMID 12024051›Full record

ArticleMolecular and cellular biology2002

Chk2 activation and phosphorylation-dependent oligomerization.

Xingzhi Xu, Lyuben M Tsvetkov, David F Stern

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
6.4field-weighted citation impact, top 2% 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

78 citing papers in PubMed, 182 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. RYBP Sensitizes Cancer Cells to PARP Inhibitors by Regulating ATM Activity.International journal of molecular sciences · 2022
    Article
  7. ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors.International journal of molecular sciences · 2022
    Review
  8. Article
  9. Review
  10. BeyondJournal of clinical medicine · 2020
    Article
  11. Article
  12. Checkpoint Responses to DNA Double-Strand Breaks.Annual review of biochemistry · 2020
    Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

18 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

3 authors at 1 institution in 1 country.

Xingzhi XuDepartment of Pathology, School of Medicine, Yale University, New Haven, Connecticut 06510, USA.
Lyuben M Tsvetkov
David F Stern
Yale University · US

Funding

PROTEIN KINASES IN YEAST DNA CHECKPOINT PATHWAYSR01CA082257 · NCI · YALE UNIVERSITY · PI STERN, DAVID F · 1999 to 2009
$2.3M
NCI NIH HHS R01 CA082257
6 · The paper itself

Abstract

The tumor suppressor gene CHK2 encodes a versatile effector serine/threonine kinase involved in responses to DNA damage. Chk2 has an amino-terminal SQ/TQ cluster domain (SCD), followed by a forkhead-associated (FHA) domain and a carboxyl-terminal kinase catalytic domain. Mutations in the SCD or FHA domain impair Chk2 checkpoint function. We show here that autophosphorylation of Chk2 produced in a cell-free system requires trans phosphorylation by a wortmannin-sensitive kinase, probably ATM or ATR. Both SQ/TQ sites and non-SQ/TQ sites within the Chk2 SCD can be phosphorylated by active Chk2. Amino acid substitutions in the SCD and the FHA domain impair auto- and trans-kinase activities of Chk2. Chk2 forms oligomers that minimally require the FHA domain of one Chk2 molecule and the SCD within another Chk2 molecule. Chk2 oligomerization in vivo increases after DNA damage, and when damage is induced by gamma irradiation, this increase requires ATM. Chk2 oligomerization is phosphorylation dependent and can occur in the absence of other eukaryotic proteins. Chk2 can cross-phosphorylate another Chk2 molecule in an oligomeric complex. Induced oligomerization of a Chk2 chimera in vivo concomitant with limited DNA damage augments Chk2 kinase activity. These results suggest that Chk2 oligomerization regulates Chk2 activation, signal amplification, and transduction in DNA damage checkpoint pathways.

Indexed as

AnimalsAtaxia Telangiectasia Mutated ProteinsBinding SitesCell Cycle ProteinsCell-Free SystemCells, CulturedCheckpoint Kinase 2DNA-Binding ProteinsDNA DamageEnzyme ActivationFibroblastsGenes, Tumor SuppressorHumansMutationPhosphorylationProtein KinasesAtaxia Telangiectasia Mutated ProteinsATM protein, humanCell Cycle ProteinsCheckpoint Kinase 2CHEK2 protein, humanDNA-Binding ProteinsProtein KinasesProtein Serine-Threonine KinasesRecombinant ProteinsTumor Suppressor Proteins

Identifiers

PMID12024051
PMCPMC133858
OpenAlexW2170595661

What OpenQuestion holds

Textmetadata
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.