Cervical carcinomas result from cellular transformation by the human 
papillomavirus (HPV) E6 and E7 oncogenes which are constitutively expressed in 
cancer cells. The E6 oncogene degrades p53 thereby modulating a large set of p53 
target genes as shown previously in the cervical carcinoma cell line HeLa. Here 
we show that the TAp63β isoform of the p63 transcription factor is also a target 
of E6. The p63 gene plays an essential role in skin homeostasis and is expressed 
as at least six isoforms. One of these isoforms, ΔNp63α, has been found 
overexpressed in squamous cell carcinomas and is shown here to be constitutively 
expressed in Caski cells associated with HPV16. We therefore explored the role 
of p63 in these cells by performing microarray analyses after repression of 
endogenous E6/E7 expression. Upon repression of the oncogenes, a large set of 
p53 target genes was found activated together with many p63 target genes related 
to cell adhesion. However, through siRNA silencing and ectopic expression of 
various p63 isoforms we demonstrated that TAp63β is involved in activation of 
this cell adhesion pathway instead of the constitutively expressed ΔNp63α and β. 
Furthermore, we showed in cotransfection experiments, combined with E6AP siRNA 
silencing, that E6 induces an accelerated degradation of TAp63β although not 
through the E6AP ubiquitin ligase used for degradation of p53. Repression of E6 
transcription also induces stabilization of endogenous TAp63β in cervical 
carcinoma cells that lead to an increased concentration of focal adhesions at 
the cell surface. Consequently, TAp63β is the only p63 isoform suppressed by E6 
in cervical carcinoma as demonstrated previously for p53. Down-modulation of 
focal adhesions through disruption of TAp63β therefore appears as a novel 
E6-dependent pathway in transformation. These findings identify a major 
physiological role for TAp63β in anchorage independent growth that might 
represent a new critical pathway in human carcinogenesis.