CoChat
Sign Up
Cited by 221Cancer-related Molecular PathwaysCell death mechanisms and regulationGenomics and Chromatin Dynamics

Negative regulation of bcl-2 expression by p53 in hematopoietic cells

Wu, Yu-ling, Mehew, John W, Heckman, Caroline A, Arcinas, Magdalena, Boxer, Linda M·2001·Oncogene
DOI 10.1038/sj.onc.1204067
Open this paper in CoChat — free account

Abstract

The p53 protein activates promoters containing p53 binding sites, and it represses other promoters. We examined the effect of p53 on bcl-2 expression in both the DHL-4 B cell line and the K562 erythroleukemia line. Transient transfection analyses revealed that wild-type p53 repressed the bcl-2 full-length promoter. The region of the bcl-2 promoter that was responsive to p53 was mapped to the bcl-2 P2 minimal promoter region, and we showed that p53 and the TATA binding protein bound to the bcl-2 TATA sequence. The TATA binding protein, p53, histone deacetylase-1 and mSin3a could be co-immunoprecipitated from K562 cell nuclear extract. The TATA binding protein and mSin3a could be recovered in a complex at the bcl-2 promoter TATA sequence, however, the formation of this complex was not dependent on the presence of p53. Treatment of K562 cells with the histone deacetylase inhibitor, trichostatin A, resulted in an increase in bcl-2 promoter activity whether p53 was present or not. Therefore, we demonstrated that p53 and the histone deacetylases repress the bcl-2 promoter independently. Similar results were obtained when endogenous bcl-2 mRNA or protein levels were measured in response to either p53 or trichostatin A, and p53 expression resulted in enhanced apoptosis. RNase protection assays demonstrated that transcription from the endogenous 3' bcl-2 promoter was decreased by p53. The regions of p53 that were required for repression of the bcl-2 promoter were defined. We conclude that the TATA sequence in the bcl-2 P2 minimal promoter is the target for repression by p53, and that the interaction between p53 and TBP is most likely responsible for the repression. Mutation of p53 may play a role in the up-regulation of bcl-2 expression in some B cell lymphomas.

Integrity signals

Registry

Crossref · 10.1038/sj.onc.1204067

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • BCL2 and BID are reported as p53 targets but are not directly regulated by p53 according to meta-analysis data.

    “Additional BCL-2 family members reported as p53 targets include BCL2190, 191 and BID192—but these are not directly regulated by p53 according to meta-analysis data18 (Supplementary Table S2).”

    From Census and evaluation of p53 target genes (2017) · cites this paper as [191]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Wu, Y.-L., Mehew, J. W., Heckman, C. A., Arcinas, M., & Boxer, L. M.
Affiliations
Stanford Medicine (US)
ORCID
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2001-01-11
Volume
20
Issue
2
Pages
240-251
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
DOI
10.1038/sj.onc.1204067
OpenAlex
W1980891354
Cited by
221
References
57
Citations by year
2026: 2 · 2025: 7 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 6 · 2019: 8 · 2018: 8 · 2017: 9 · 2016: 9 · 2015: 12 · 2014: 11 · 2013: 9 · 2012: 14
FWCI
5.88
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (CA56764)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
p53, Bcl-2, transcriptional repression, TATA-binding protein, HDAC1, mSin3A, Bcl-2 promoter, trichostatin A, apoptosis, hematopoietic cells, B-cell lymphoma, TP53 mutation
MeSH terms
B-Lymphocytes, Cells, Cultured, DNA-Binding Proteins, Enzyme Inhibitors, Leukemia, Erythroblastic, Acute, Gene Expression Regulation, Hematopoietic Stem Cells, Histone Deacetylases, Humans, Hydroxamic Acids, Promoter Regions, Genetic, Repressor Proteins, Transcription Factors, Down-Regulation, Tumor Suppressor Protein p53, Apoptosis, Protein Structure, Tertiary, Proto-Oncogene Proteins c-bcl-2, Response Elements, TATA-Box Binding Protein, Sin3 Histone Deacetylase and Corepressor Complex, Histone Deacetylase 1, Histone Deacetylase Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review