p53 family members with a transactivation (TA) domain induce cell cycle arrest 
and promote apoptosis. However, DeltaNp63 isotypes lacking the TA-domain promote 
cell proliferation and tumorigenesis in vitro and in vgammavo. Although p53, 
TAp63 or TAp73 are stabilized upon DNA damage, we found that the genotoxic 
stress agents induced a dramatic decrease and phosphorylation of DeltaNp63alpha 
in squamous cell carcinoma cells. Further work revealed that RACK1 physically 
associated with the p63alpha C-terminal domain through its WD40 domain. However, 
stratifin binds with phosphorylated DeltaNp63alpha in response to cisplatin. 
Upon DNA damage induced by cisplatin, stratifin mediated a nuclear export of 
DeltaNp63alpha into cytoplasm and then RACK1 targeted latter into a proteasome 
degradation pathway possibly serving as an E3 ubiquitin ligase. Moreover, siRNA 
knockdown of both stratifin and RACK1 inhibited a nuclear export and protein 
degradation of DeltaNp63alpha, respectively. Our data suggest that modification 
and down regulation of DeltaNp63alpha is one of the major determinants of the 
cellular response to DNA damage in human head and neck cancers.