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S100A2 gene is a direct transcriptional target of p53 homologues during keratinocyte differentiation

Oncogene volume 25, pages 3628–3637 (2006)Cite this article

Abstract

The p53 paralogues p73, p63 and their respective truncated isoforms have been shown to be critical regulators of developmental and differentiation processes. Indeed, both p73- and p63-deficient mice exhibit severe developmental defects. Here, we show that S100A2 gene, whose transcript and protein are induced during keratinocyte differentiation of HaCaT cells, is a direct transcriptional target of p73β and ΔNp63α and is required for proper keratinocyte differentiation. Transactivation assays reveal that p73β and ΔNp63α exert opposite transcriptional effects on S100A2 gene. While ΔNp63α is found in vivo onto S100A2 regulatory regions predominantly in proliferating cells, p73β is recruited in differentiating cells. Silencing of p73 impairs the induction of S100A2 during the differentiation of HaCaT cells. Moreover, silencing of p73 or S100A2 impairs the proper expression of keratinocyte differentiation markers. Of note, p53 family members do not trigger S100A2 gene expression in response to apoptotic doses of cisplatin and doxorubicin.

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Acknowledgements

We thank Dr R Agami and Dr A Costanzo for plasmids, antibodies and helpful suggestions. This work was supported by Telethon (no.GGP030358), Italian Association for Cancer Research to GB and SS (AIRC); Ministero della Salute; MIUR-FIRB Italy; Italia-USA and EC FP6 funding (Contract 503576). This publication reflects the authors' views and not necessarily those of the European Community. The EC is not liable for any use that may be made of the information contained herein.

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Author notes

  1. E Lapi and A Iovino: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy

    E Lapi, A Iovino, G Fontemaggi, A R Soliera, S Iacovelli, A Sacchi, G Blandino & S Strano

  2. Rome Oncogenomic Center, Rome, Italy

    G Fontemaggi & G Blandino

  3. Department of Pediatric Hematology-Oncology, Sheba Medical Center, Tel-Hashomer, Israel

    G Rechavi

  4. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel

    D Givol

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  1. E Lapi
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  2. A Iovino
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Correspondence to G Blandino.

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Lapi, E., Iovino, A., Fontemaggi, G. et al. S100A2 gene is a direct transcriptional target of p53 homologues during keratinocyte differentiation. Oncogene 25, 3628–3637 (2006). https://doi.org/10.1038/sj.onc.1209401

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