Evidence map›Paper›PMID 18716058›Full record

ArticleMolecular biology of the cell2008

Regulation of Chk1 by its C-terminal domain.

Ana Kosoy, Matthew J O'Connell

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

24 citing papers in PubMed, 29 citations in OpenAlex.

  1. A C-degron regulates Chk1 kinase by allowing stability of inactive Chk1 and by making it short- lived upon activation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Review
  3. Article
  4. Case report: A germlineFrontiers in oncology · 2024
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Roles of Chk1 in cell biology and cancer therapy.International journal of cancer · 2014
    Review
  13. Article
  14. Checkpoint kinase 1 in DNA damage response and cell cycle regulation.Cellular and molecular life sciences : CMLS · 2013
    Review
  15. Regulatory motifs in Chk1.Cell cycle (Georgetown, Tex.) · 2013
    Article
  16. Article
  17. Article
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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

2 authors at 1 institution in 1 country.

Ana KosoyDepartment of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
Matthew J O'Connell
Icahn School of Medicine at Mount Sinai · US

Funding

Chk1 signaling in the G2 DNA damage checkpointR01CA100076 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI O'CONNELL, MATTHEW J · 2003 to 2007
$1.7M
Chk1 signaling in the G2 DNA damage checkpointR56CA100076 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI O'CONNELL, MATTHEW J · 2009 to 2009
$336k
NCI NIH HHS CA100076NCI NIH HHS R01 CA100076NCI NIH HHS R56 CA100076
6 · The paper itself

Abstract

Chk1 is a protein kinase that is the effector molecule in the G2 DNA damage checkpoint. Chk1 homologues have an N-terminal kinase domain, and a C-terminal domain of approximately 200 amino acids that contains activating phosphorylation sites for the ATM/R kinases, though the mechanism of activation remains unknown. Structural studies of the human Chk1 kinase domain show an open conformation; the activity of the kinase domain alone is substantially higher in vitro than full-length Chk1, and coimmunoprecipitation studies suggest the C-terminal domain may contain an autoinhibitory activity. However, we show that truncation of the C-terminal domain inactivates Chk1 in vivo. We identify additional mutations within the C-terminal domain that activate ectopically expressed Chk1 without the need for activating phosphorylation. When expressed from the endogenous locus, activated alleles show a temperature-sensitive loss of function, suggesting these mutations confer a semiactive state to the protein. Intragenic suppressors of these activated alleles cluster to regions in the catalytic domain on the face of the protein that interacts with substrate, suggesting these are the regions that interact with the C-terminal domain. Thus, rather than being an autoinhibitory domain, the C-terminus of Chk1 also contains domains critical for adopting an active configuration.

Indexed as

AllelesAmino Acid SequenceAmino Acid SubstitutionAspartic AcidCheckpoint Kinase 1Conserved SequenceEnzyme ActivationG2 PhaseGenes, SuppressorGlutamic AcidMethyl MethanesulfonateMolecular Sequence DataMutant ProteinsMutationPhenotypePhosphorylationAspartic AcidCheckpoint Kinase 1CHEK1 protein, humanChk1 protein, S pombeGlutamic AcidMethyl MethanesulfonateMutant ProteinsProtein KinasesSchizosaccharomyces pombe Proteins

Identifiers

PMID18716058
PMCPMC2575178
OpenAlexW2023860520

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.