| General information | Literature | Expression | Regulation | Mutation | Homolog | Interaction |
Basic Information | |
|---|---|
Gene ID | 8626 |
Name | TP63 |
Synonymous | tumor protein p63;TP63;tumor protein p63 |
Definition | CUSP|amplified in squamous cell carcinoma|chronic ulcerative stomatitis protein|keratinocyte transcription factor KET|transformation-related protein 63|tumor protein 63|tumor protein p53-competing protein|tumor protein p63 deltaN isoform delta |
Position | 3q28 |
Gene type | protein-coding |
Title | Abstract |
| Critical and distinct roles of p16 and telomerase in regulating the proliferative life span of normal human prostate epithelial progenitor cells. | Normal human prostate (NHP) epithelial cells undergo senescence in vitro and in vivo, but the underlying molecular mechanisms remain obscure. Here we show that the senescence of primary NHP cells, which are immunophenotyped as intermediate basal-like cells expressing progenitor cell markers CD44, alpha2beta1, p63, hTERT, and CK5/CK18, involves loss of telomerase expression, up-regulation of p16, and activation of p53. Using genetically defined manipulations of these three signaling pathways, we show that p16 is the primary determinant of the NHP cell proliferative capacity and that hTERT is required for unlimited proliferative life span. Hence, suppression of p16 significantly extends NHP cell life span, but both p16 inhibition and hTERT are required to immortalize NHP cells. Importantly, immortalized NHP cells retain expression of most progenitor markers, demonstrate gene expression profiles characteristic of proliferating progenitor cells, and possess multilineage differentiation potential generating functional prostatic glands. Our studies shed important light on the molecular mechanisms regulating the proliferative life span of NHP progenitor cells. |