Repression of RNA polymerase I transcription by the tumor suppressor p53.

Abstract

The tumor suppressor protein p53 is frequently inactivated in tumors. It functions as a transcriptional activator as well as a repressor for a number of viral and cellular promoters transcribed by RNA polymerase II (Pol II) and by RNA Pol III. Moreover, it appears that p53 also suppresses RNA Pol I transcription. In this study, we examined the molecular mechanism of Pol I transcriptional inhibition by p53. We show that wild-type, but not mutant, p53 can repress Pol I transcription from a human rRNA gene promoter in cotransfection assays. Furthermore, we show that recombinant p53 inhibits rRNA transcription in a cell-free transcription system. In agreement with these results, p53-null epithelial cells display an increased Pol I transcriptional activity compared to that of epithelial cells that express p53. However, both cell lines display comparable Pol I factor protein levels. Our biochemical analysis shows that p53 prevents the interaction between SL1 and UBF. Protein-protein interaction assays indicate that p53 binds to SL1, and this interaction is mostly mediated by direct contacts with TATA-binding protein and TAF(I)110. Moreover, template commitment assays show that while the formation of a UBF-SL1 complex can partially relieve the inhibition of transcription, only the assembly of a UBF-SL1-Pol I initiation complex on the rDNA promoter confers substantial protection against p53 inhibition. In summary, our results suggest that p53 represses RNA Pol I transcription by directly interfering with the assembly of a productive transcriptional machinery on the rRNA promoter.

• Authors: W Zhai, L Comai
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 20 Issue 16 Pg. 5930-8 (Aug 2000) ISSN: 0270-7306 [Print] United States
• PMID: 10913176 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Tumor Suppressor Protein p53
• RNA Polymerase I

Topics

• Genes, Tumor Suppressor
• Genes, p53
• HeLa Cells
• Humans
• Plasmids
• RNA Polymerase I (genetics)
• Transcription, Genetic
• Transfection
• Tumor Suppressor Protein p53 (genetics)