Evidence map›Paper›PMID 32001619›Full record

ArticleThe Journal of biological chemistry2020

The GTPase KRAS suppresses the p53 tumor suppressor by activating the NRF2-regulated antioxidant defense system in cancer cells.

Hua Yang, Shengyan Xiang, Aslamuzzaman Kazi, Said M Sebti

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

18 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Resistance to mutant KRASExperimental cell research · 2022
    Article
  11. Article
  12. Review on the Synthesis and Therapeutic Potential of Pyrido[2,3-Pharmaceuticals (Basel, Switzerland) · 2022
    Review
  13. Effect ofFrontiers in cell and developmental biology · 2022
    Article
  14. Review
  15. Review
  16. NRF2 and Primary Cilia: An Emerging Partnership.Antioxidants (Basel, Switzerland) · 2020
    Review
  17. Review
  18. Review
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 2 institutions in 1 country.

Hua YangDrug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 Department of Oncologic Sciences, University of South Florida, Tampa, Florida 33612.
Shengyan XiangDrug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 Department of Oncologic Sciences, University of South Florida, Tampa, Florida 33612.
Aslamuzzaman KaziDrug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 Department of Oncologic Sciences, University of South Florida, Tampa, Florida 33612.
Said M SebtiDrug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 Department of Oncologic Sciences, University of South Florida, Tampa, Florida 33612. Electronic address: Said.Sebti@vcuhealth.org.
Moffitt Cancer Center · USUniversity of South Florida · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
Targeting Mutant KRAS for Cancer TherapyR35CA197731 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SEBTI, SAID M · 2016 to 2022
$6.2M
NCI NIH HHS P30 CA076292NCI NIH HHS R35 CA197731
6 · The paper itself

Abstract

In human cancer cells that harbor mutant KRAS and WT p53 (p53), KRAS contributes to the maintenance of low p53 levels. Moreover, KRAS depletion stabilizes and reactivates p53 and thereby inhibits malignant transformation. However, the mechanism by which KRAS regulates p53 is largely unknown. Recently, we showed that KRAS depletion leads to p53 Ser-15 phosphorylation (P-p53) and increases the levels of p53 and its target p21/WT p53-activated fragment 1 (WAF1)/CIP1. Here, using several human lung cancer cell lines, siRNA-mediated gene silencing, immunoblotting, quantitative RT-PCR, promoter-reporter assays, and reactive oxygen species (ROS) assays, we demonstrate that KRAS maintains low p53 levels by activating the NRF2 (NFE2-related factor 2)-regulated antioxidant defense system. We found that KRAS depletion led to down-regulation of NRF2 and its targets NQO1 (NAD(P)H quinone dehydrogenase 1) and SLC7A11 (solute carrier family 7 member 11), decreased the GSH/GSSG ratio, and increased ROS levels. We noted that the increase in ROS is required for increased P-p53, p53, and p21

Indexed as

Amino Acid Transport System y+AntioxidantsCell Line, TumorCyclin-Dependent Kinase Inhibitor p21Down-RegulationGlutathioneGlutathione DisulfideHumansNAD(P)H Dehydrogenase (Quinone)NF-E2-Related Factor 2PhosphorylationProtein Serine-Threonine KinasesProto-Oncogene MasProto-Oncogene Proteins p21(ras)ral GTP-Binding ProteinsReactive Oxygen SpeciesAmino Acid Transport System y+AntioxidantsCyclin-Dependent Kinase Inhibitor p21GlutathioneGlutathione DisulfideKRAS protein, humanMAS1 protein, humanNAD(P)H Dehydrogenase (Quinone)NF-E2-Related Factor 2NQO1 protein, humanProtein Serine-Threonine KinasesProto-Oncogene MasProto-Oncogene Proteins p21(ras)Ralb protein, humanral GTP-Binding ProteinsReactive Oxygen SpeciesRNA, Small InterferingSLC7A11 protein, humanTBK1 protein, humanTP53 protein, humanTumor Suppressor Protein p53GTPase Kras (KRAS)nuclear factor 2 (erythroid-derived 2-like factor) (NFE2L2) (Nrf2)p53RalBreactive oxygen species (ROS)redox signalingTBK1

Identifiers

PMID32001619
PMCPMC7062149
OpenAlexW3003234363

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.