Evidence map›Paper›PMID 27979966›Full record

ArticleThe Journal of biological chemistry2017

Insulin-like Growth Factor 1 Receptor Signaling Is Required for Optimal ATR-CHK1 Kinase Signaling in Ultraviolet B (UVB)-irradiated Human Keratinocytes.

Michael G Kemp, Dan F Spandau, Richard Simman, Jeffrey B Travers

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

20 citing papers in PubMed, 29 citations in OpenAlex.

  1. Trial
  2. Article
  3. Translesion Synthesis DNA Polymerase Gene Expression Is Impacted by Age and IGF-1 in Epidermal Human Skin.JID innovations : skin science from molecules to population health · 2025
    Article
  4. Antioxidant and Anti-Inflammatory Effects of CrudeAntioxidants (Basel, Switzerland) · 2025
    Article
  5. New concepts on abnormal UV reactions in systemic lupus erythematosus and a screening tool for assessment of photosensitivity.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2023
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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

4 authors at 3 institutions in 1 country.

Michael G KempFrom the Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, Ohio 45435, mike.kemp@wright.edu.
Dan F Spandauthe Departments of Dermatology and.
Richard SimmanFrom the Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, Ohio 45435.
Jeffrey B TraversFrom the Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, Ohio 45435.
Wright State University · USDayton VA Medical Center · USIndiana University School of Medicine

Funding

Wounding Therapy and PhotocarcinogenesisR01AG048946 · NIA · WRIGHT STATE UNIVERSITY · PI SPANDAU, DAN F, TRAVERS, JEFFREY B. · 2014 to 2024
$2.9M
Mechanisms of photocarcinogenesis in geriatric skinR01ES020866 · NIEHS · INDIANA UNIVERSITY INDIANAPOLIS · PI SPANDAU, DAN F, TRAVERS, JEFFREY B. · 2012 to 2016
$1.7M
IGF-1 and the initiation of non-melanoma skin cancerI01CX000809 · VA · RLR VA MEDICAL CENTER · PI TRAVERS, JEFFREY B. · 2014 to 2016
–
CSRD VA I01 CX000809NIA NIH HHS R01 AG048946NIEHS NIH HHS R01 ES020866
6 · The paper itself

Abstract

UVB wavelengths of light induce the formation of photoproducts in DNA that are potentially mutagenic if not properly removed by the nucleotide excision repair machinery. As an additional mechanism to minimize the risk of mutagenesis, UVB-irradiated cells also activate a checkpoint signaling cascade mediated by the ATM and Rad3-related (ATR) and checkpoint kinase 1 (CHK1) kinases to transiently suppress DNA synthesis and cell cycle progression. Given that keratinocytes in geriatric skin display reduced activation of the insulin-like growth factor 1 receptor (IGF-1R) and alterations in DNA repair rate, apoptosis, and senescence following UVB exposure, here we used cultured human keratinocytes in vitro and skin explants ex vivo to examine how IGF-1R activation status affects ATR-CHK1 kinase signaling and the inhibition of DNA replication following UVB irradiation. We find that disruption of IGF-1R signaling with small-molecule inhibitors or IGF-1 withdrawal partially abrogates both the phosphorylation and activation of CHK1 by ATR and the accompanying inhibition of chromosomal DNA synthesis in UVB-irradiated keratinocytes. A critical protein factor that mediates both ATR-CHK1 signaling and nucleotide excision repair is replication protein A, and we find that its accumulation on UVB-damaged chromatin is partially attenuated in cells with an inactive IGF-1R. These results indicate that mutagenesis and skin carcinogenesis in IGF-1-deficient geriatric skin may be caused by defects in multiple cellular responses to UVB-induced DNA damage, including through a failure to properly suppress DNA synthesis on UVB-damaged DNA templates.

Indexed as

Skin AgingAtaxia Telangiectasia Mutated ProteinsCheckpoint Kinase 1DNA ReplicationHumansKeratinocytesReceptor, IGF Type 1Receptors, SomatomedinReplication Protein ASignal TransductionSkinUltraviolet RaysAtaxia Telangiectasia Mutated ProteinsATR protein, humanCheckpoint Kinase 1CHEK1 protein, humanIGF1R protein, humanReceptor, IGF Type 1Receptors, SomatomedinReplication Protein Acell signalingcheckpoint controlDNA damageDNA damage responseDNA repairDNA replicationkeratinocytenucleotide excision repairprotein kinaseskin

Identifiers

PMID27979966
PMCPMC5270469
OpenAlexW2576231494

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.