TAp63-mediated senescence overrides Ras-driven transformation of p53-deficient cells, preventing tumour initiation, and doxycycline-regulated expression of TAp63 activates p21 Waf/Cip1, induces senescence and inhibits progression of established tumours in vivo.

All isoforms of TAp63 transactivate the p21-encoding gene, with TAp63β showing the highest levels of p21 induction (Helton et al., 2008). The transcriptional activation of p21 by TAp63 requires both the AD and proline-rich domains of TAp63.

TAp63-mediated senescence overrides Ras-driven transformation of p53-deficient cells, preventing tumour initiation, and doxycycline-regulated expression of TAp63 activates p21(Waf/Cip1), induces senescence and inhibits progression of established tumours in vivo.

We found that downregulation of p53, p63 and TAp63 decreases the expression of growth-suppressing genes, including p21, PUMA and MIC-1. Interestingly, downregulation of p63, particularly TAp63, but not p53, disrupts the ability of MDCK cells to form a cyst structure in 3-D culture via heightened epithelial-to-mesenchymal transition (EMT).

Nov 28, 2018 · p53, with its family members p63 and p73, have been shown to promote myoblast differentiation by regulation of the function of the retinoblastoma protein and by direct activation of p21 Cip/Waf1 and p57 Kip2, promoting cell cycle exit.

Apr 23, 2019 · We selected microRNA 130b (miR-130b), a direct downstream target that is transcriptionally activated by the transactivation (TA) domain of tumor protein p63 (TAp63), as a candidate tumor-suppressor microRNA that has the potential to overcome mutations in p53 by activating the TAp63 pathway.

We observed that down-regulation of ΔNp63 or all p63 isoforms, but not TAp63, led to substantial cellular senescence, associated with increased expression of p21 and lack of induction of p16. This result suggests that down-regulation of p63 or ΔNp63 in cells led to increased senescence.

Thus, TAp63 has an activity similar to p53, such as in inducing p21 [3]. ΔNp63 lacks the activation domain conserved in p53 but carries a unique activation domain in the N-terminus, which is composed of 14 unique N-terminal residues and the proline-rich domain [4].

Apr 1, 2013 · We found that like downregulation of p53, downregulation of p63 and TAp63 decreases expression of growth-suppressing genes, including p21, PUMA and MIC-1, and consequently promotes cell...

Jan 15, 2015 · We propose that the p63 C-terminus links cell cycle control and the proliferative potential of epidermal progenitor cells via mechanisms that equilibrate TAp63 and ΔNp63 isoform function.