S100A2 gene is a direct transcriptional target of p53 homologues during keratinocyte differentiation.
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 p73beta and DeltaNp63alpha and is required for proper keratinocyte differentiation. Transactivation assays reveal that p73beta and DeltaNp63alpha exert opposite transcriptional effects on S100A2 gene. While DeltaNp63alpha is found in vivo onto S100A2 regulatory regions predominantly in proliferating cells, p73beta 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.
Lapi
E
E
Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy.
Iovino
A
A
Fontemaggi
G
G
Soliera
A R
AR
Iacovelli
S
S
Sacchi
A
A
Rechavi
G
G
Givol
D
D
Blandino
G
G
Strano
S
S
D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000235:genetics* / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D005786:Gene Expression Regulation; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D009418:S100 Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D002630:Chemotactic Factors; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009418:S100 Proteins; C098997:S100A2 protein, human; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004317:Doxorubicin; D002945:Cisplatin