Dysregulation of TAp63 mRNA and Protein Levels in Psoriasis

Abstract

Psoriasis is a chronic and excessive inflammation of the skin and is currently incurable. The cause of psoriasis remains poorly understood and a central and cooperative role for keratinocytes and T-cells in triggering the disease is highlighted. The p63 gene encodes six different proteins with homology to the tumor suppressor protein p53 that are crucial for normal development of ectodermally derived structures such as skin and oral mucosa. In this study, we have analyzed levels of the different p63 isoforms using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in 15 patients diagnosed with psoriasis. Quantitative RT-PCR results showed downregulation of the full-length TAp63 in psoriatic lesions compared to both clinically normal skin from patients (P<0.001) and matched healthy controls (P<0.001); however, p63 protein levels detected by immunohistochemistry were similar. All psoriasis lesions also had detectable levels of activated Stat3, a protein indicated in development of the disease, whereas control tissue lacked this protein. The present data show a different regulation of TAp63 in psoriasis, where the discrepancy between mRNA levels and protein expression indicates a post-transcriptional regulation analogous to that seen in p53.

p63 in epithelial development

“…Expression of the full-length TAp63 mRNA has also been described [23,24] and some studies, using not commercially available specific anti-TAp63 antibodies, have detected TAp63 proteins in adult epidermis [22,25]. The TAp63 isoform has also been shown to be constitutively expressed in female germ cells during meiotic arrest, and is essential (after post-translational modification) for DNA damage-induced oocyte death independently of p53 [15].…”

Regulation of skin aging and heart development by TAp63

“…48 In this regard, the TAp63 À/À mice display a phenotype similar to defects in humans with Hay-Wells syndrome where patients with mutations in p63 develop dermatitis and alopecia. 49 We suggest that these patients have defects in dermal stem cell maintenance, which we propose could be reversed by drug discovery efforts that enhance dermal stem cell or SKPs self-renewal.…”

TAp63 and ΔNp63 in Cancer and Epidermal Development

“…1,27,59 Expression of the full-length TAp63 mRNA is also seen, 58,59 and TAp63 proteins are found in epidermis. 27,61 Differential function of p63 isoforms in epidermal formation. Since the publication of the two p63 -/-studies, it has become clear that p63 is a "master gene" for epidermal development, 5,6,62 see fig.…”