A mutant version of p53 (p53-121F), in which phenylalanine replaces the 121st 
serine residue, can induce apoptosis more effectively than wild-type p53 
(wt-p53). In view of this observation, we considered that one or more 
apoptosis-related p53-target genes might be preferentially induced by p53-121F. 
We carried out cDNA microarray analysis to identify such genes, using mRNAs 
isolated from LS174T colon-cancer cells infected by adenovirus vectors 
containing either p53-121F (Ad-p53-121F) or wt-p53 (Ad-p53). The STAG1 gene was 
one of the transcripts showing higher expression levels in cells infected with 
Ad-p53-121F as opposed to Ad-wtp53. The encoded product appears to contain a 
transmembrane domain, and binding motifs for SH3 and WW. In two other cancer 
cell lines, the expression of STAG1 mRNA was induced in response to various 
genotoxic stresses in a p53-dependent manner; moreover, enforced expression of 
STAG1 led to apoptosis in several additional cancer cell lines. Suppression of 
endogenous STAG1 using the RNA-interference method reduced the apoptotic 
response, whether induced by Ad-p53-121F or Ad-p53. These results suggest that 
STAG1, a novel transcriptional target for p53, mediates p53-dependent apoptosis, 
and might be a good candidate for next-generation gene therapy.