Tumor protein p63, referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 (also known as the p63) gene.

Chromosome 3 (human)

The TP63 gene, p53 tumor suppressor gene and along with p73 constitutes the p53 gene family based on their structural similarity.

Tumor protein p63 is a member of the p53 family of transcription factors. 

TP63 encodes for two main isoforms by alternative promoters (TAp63 and ΔNp63). 

ΔNp63 is involved in multiple functions during skin development and in adult stem/progenitor cell regulation.

TAp63 has been mostly restricted to its apoptotic function and more recently as the guardian of oocyte integrity.

TP63 can also regulate PERP expression with TP53 in human cancer.

At least 42 disease-causing mutations in  TP 63gene have been discovered.

TP63 mutations associated with several malformation syndromes:  cleft lip and/or palate, ectrodactyly-ectodermal dysplasia-cleft syndrome, ankyloblepharon-ectodermal dysplasia-cleft lip/palate or Hay–Wells syndrome in which a midline cleft lip is also a common feature, Acro–dermato–ungual–lacrimal–tooth syndrome (ADULT); limb-mammary syndrome; Rap-Hodgkin syndrome (RHS); and orofacial cleft.

p63 transcription factor is a key regulator of epidermal keratinocyte proliferation and differentiation. 

TP63 is overexpressed in vulvar squamous cell carcinoma.

p63 immunostaining has utility for differentiating prostatic adenocarcinoma and benign prostatic tissue: normal prostatic glands stain with p63 while the malignant glands in prostatic adenocarcinoma do not.

P63 is also helpful in distinguishing poorly differentiated squamous cell carcinoma from small cell carcinoma or adenocarcinoma: P63 is strongly stained in poorly differentiated squamous cell, but negative in small cell or adenocarcinoma.

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