We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Oncogene | Jan 11, 2001

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.

Pubmed ID: 11313951 RIS Download

Mesh terms: Apoptosis | B-Lymphocytes | Cells, Cultured | DNA-Binding Proteins | Down-Regulation | Enzyme Inhibitors | Gene Expression Regulation | Hematopoietic Stem Cells | Histone Deacetylase 1 | Histone Deacetylase Inhibitors | Histone Deacetylases | Humans | Hydroxamic Acids | Leukemia, Erythroblastic, Acute | Promoter Regions, Genetic | Protein Structure, Tertiary | Proto-Oncogene Proteins c-bcl-2 | Repressor Proteins | Response Elements | TATA-Box Binding Protein | Transcription Factors | Tumor Suppressor Protein p53

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: CA56764

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.