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Diverse p63 and p73 isoforms regulate Δ133p53 expression through modulation of the internal TP53 promoter activity.
- Source :
-
Cell death and differentiation [Cell Death Differ] 2012 May; Vol. 19 (5), pp. 816-26. Date of Electronic Publication: 2011 Nov 11. - Publication Year :
- 2012
-
Abstract
- In response to stress, p53 binds and transactivates the internal TP53 promoter, thus regulating the expression of its own isoform, Δ133p53α. Here, we report that, in addition to p53, at least four p63/p73 isoforms regulate Δ133p53 expression at transcriptional level: p63β, ΔNp63α, ΔNp63β and ΔNp73γ. This regulation occurs through direct DNA-binding to the internal TP53 promoter as demonstrated by chromatin immunoprecipitation and the use of DNA-binding mutant p63. The promoter regions involved in the p63/p73-mediated transactivation were identified using deleted, mutant and polymorphic luciferase reporter constructs. In addition, we observed that transient expression of p53 family members modulates endogenous Δ133p53α expression at both mRNA and protein levels. We also report concomitant variation of p63 and Δ133p53 expression during keratinocyte differentiation of HaCat cells and induced pluripotent stem cells derived from mutated p63 ectodermal dysplasia patients. Finally, proliferation assays indicated that Δ133p53α isoform regulates the anti-proliferative activities of p63β, ΔNp63α, ΔNp63β and ΔNp73γ. Overall, this study shows a strong interplay between p53, p63 and p73 isoforms to orchestrate cell fate outcome.
- Subjects :
- Blotting, Western
Cell Line
Cell Line, Tumor
Cell Proliferation
Chromatin Immunoprecipitation
DNA-Binding Proteins genetics
Humans
Nuclear Proteins genetics
Protein Isoforms genetics
Real-Time Polymerase Chain Reaction
Transcription Factors genetics
Tumor Protein p73
Tumor Suppressor Proteins genetics
DNA-Binding Proteins metabolism
Nuclear Proteins metabolism
Promoter Regions, Genetic genetics
Protein Isoforms metabolism
Transcription Factors metabolism
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5403
- Volume :
- 19
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell death and differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 22075982
- Full Text :
- https://doi.org/10.1038/cdd.2011.152