Tumor protein p63 (TP63)

Tumor protein p63 (TP63) is a transcription factor in the p53 family, known for its crucial roles in epithelial development, stem/progenitor cell maintenance, cell differentiation, and apoptosis[1][2][3]. It is encoded by the TP63 gene and is essential for proper development of skin, limbs, craniofacial structures, and epithelial tissues. TP63 produces multiple isoforms via alternative promoter usage and splicing, notably TAp63 (involved in apoptosis, especially in oocyte quality control and integrity) and ΔNp63 (prominent in epidermal development and stem cell maintenance). TP63 is widely recognized as a diagnostic biomarker in pathology (notably squamous cell carcinoma) and is genetically implicated in various developmental syndromes and cancers. While not the direct target of approved drugs, its isoforms mediate sensitivity and response to certain chemotherapeutic agents, and the protein’s essential roles pose potential therapeutic and safety challenges[1][2][3].

Other names

Transformation-related protein 63P63P73LTP73LKETp51p73HAISB(p51A)B(p51B)CUSPEEC3LMSNBPOFC8p40p73LRHSSHFM4TP53CPTP53LTumor protein p73-likeTumor protein 63Amplified in squamous cell carcinomaChronic ulcerative stomatitis proteinKeratinocyte transcription factor KETTumor protein p53-competing protein

Modulation of isoform expression (e.g., DNA damage induces TAp63-dependent apoptosis, degradation or stabilization of ΔNp63 by phosphorylation, ubiquitination, or proteasomal degradation). Chemotherapy agents (e.g., cisplatin) can stabilize or degrade different TP63 isoforms depending on context. Currently, no approved drugs specifically and directly target TP63, but it is involved in chemoresistance and sensitivity.