Evidence map›Paper›PMID 19846904›Full record

ArticleAnticancer research2009

p53-Mediated down-regulation of the human DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) via interaction with Sp1 transcription factor.

Dora Bocangel, Shiladitya Sengupta, Sankar Mitra, Kishor K Bhakat

Open access · greenAbstract read
In one paragraph

Article in Anticancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 12% 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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. DNA Alkylation Damage by Nitrosamines and Relevant DNA Repair Pathways.International journal of molecular sciences · 2023
    Review
  10. Molecular and Circulating Biomarkers in Patients with Glioblastoma.International journal of molecular sciences · 2022
    Review
  11. OWorld journal of gastrointestinal oncology · 2022
    Article
  12. Article
  13. Article
  14. Genomic Space ofInternational journal of molecular sciences · 2021
    Article
  15. Article
  16. Article
  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

4 authors at 1 institution in 1 country.

Dora BocangelDepartment of Biochemistry, University of Texas Medical Branch, Galveston, TX 77555, USA.
Shiladitya Sengupta
Sankar Mitra
Kishor K Bhakat
The University of Texas Medical Branch at Galveston · US

Funding

STRUCTURE AND REGULATION OF DNA REPAIR GENES OF MAMMALSR01CA053791 · NCI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI MITRA, SANKAR · 1991 to 2011
$4.0M
REGULATION OF ALKYLATION DAMAGE REPAIR GENES OF MAMMALSR01ES007572 · NIEHS · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI MITRA, SANKAR · 1995 to 1998
–
NCI NIH HHS R01 CA053791NCI NIH HHS R01 CA53791NIEHS NIH HHS P50 ES66076NIEHS NIH HHS R01 ES007572NIEHS NIH HHS R01 ES07572
6 · The paper itself

Abstract

O(6)-Methylguanine-DNA methyltransferase (MGMT), a ubiquitous DNA repair protein, reverses mutagenic and cytotoxic effects of O(6)-alkylguanine in DNA induced by chemotherapeutic N-alkyl N-nitrosourea and procarbazine type drugs by dealkylating the adduct. MGMT expression is down-regulated by wild-type p53 (WTp53) in human tumor cells. Here we report that p53 sequesters the Sp1 transcription factor to prevent its binding to the cognate cis elements in the MGMT promoter and thus inhibits MGMT expression. Sp1 overexpression abrogated the inhibitory effect of p53 on the MGMT promoter activity in a dose-dependent manner. Stable interaction of Sp1 with WTp53 was observed in HCT116 cells. Moreover, WTp53 overexpression reduced the binding of the nuclear extract to the Sp1 consensus sequence, even though recombinant p53 alone did not bind to the same sequence. Taken together, these results suggest that sequestration of Sp1 could be one of the mechanisms by which p53 negatively regulates MGMT expression, thus enhancing sensitivity of tumor cells to O(6)-alkylguanine generating drugs.

Indexed as

DNA RepairAntineoplastic Agents, AlkylatingColonic NeoplasmsConsensus SequenceDacarbazineDown-RegulationGlioblastomaHCT116 CellsHumansLung NeoplasmsO(6)-Methylguanine-DNA MethyltransferasePromoter Regions, GeneticProtein BindingSp1 Transcription FactorTemozolomideTumor Suppressor Protein p53Antineoplastic Agents, AlkylatingDacarbazineO(6)-Methylguanine-DNA MethyltransferaseSp1 Transcription FactorTemozolomideTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID19846904
PMCPMC2814523
OpenAlexW2137576936

What OpenQuestion holds

Textmetadata
LicenceTDM
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.