Abstract
Since the discovery of the TP63 gene in 1998, many studies have demonstrated that ΔNp63, a p63 isoform of the p53 gene family, is involved in multiple functions during skin development and in adult stem/progenitor cell regulation. In contrast, TAp63 studies have been mostly restricted to its apoptotic function and more recently as the guardian of oocyte integrity. TAp63 endogenous expression is barely detectable in embryos and adult (except in oocytes), presumably because of its rapid degradation and the lack of antibodies able to detect weak expression. Nevertheless, two recent independent studies have demonstrated novel functions for TAp63 that could have potential implications to human pathologies. The first discovery is related to the protective role of TAp63 on premature aging. TAp63 controls skin homeostasis by maintaining dermal and epidermal progenitor/stem cell pool and protecting them from senescence, DNA damage and genomic instability. The second study is related to the role of TAp63, expressed by the primitive endoderm, on heart development. This unexpected role for TAp63 has been discovered by manipulation of embryonic stem cells in vitro and confirmed by the severe cardiomyopathy observed in brdm2 p63-null embryonic hearts. Interestingly, in both cases, TAp63 acts in a cell-nonautonomous manner on adjacent cells. Here, we discuss these findings and their potential connection during development.
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Abbreviations
- SKPs:
-
skin-derived precursors
- TAp63:
-
p63 containing the transactivation domain
- ΔNp63:
-
amino-deleted p63 isoform
- ES cells:
-
embryonic stem cells
- Ebs:
-
embryoid bodies
- T Bry:
-
T-box transcription factor brachyury
- Mesp1:
-
mesoderm posterior1
- Isel1:
-
Islet-1
- Chip:
-
chromatin immunoprecipitation
- TF:
-
transcription factor
- ED:
-
ectodermal dysplasia syndromes
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Acknowledgements
We thank David Kaplan, Ruby Shalom-Feuerstein and Wim Declercq for their comments, suggestions and criticisms. Part of this work was supported for DA by the Sixth EEC Framework Program within the EPISTEM project (LSHB-CT-2005-019067), the Agence Nationale pour la Recherche (ANR BLANC 06 and GENOPAT 08) and the Israel Science Foundation.
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Paris, M., Rouleau, M., Pucéat, M. et al. Regulation of skin aging and heart development by TAp63. Cell Death Differ 19, 186–193 (2012). https://doi.org/10.1038/cdd.2011.181
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DOI: https://doi.org/10.1038/cdd.2011.181
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