The p73 gene possesses an extrinsic P1 promoter and an intrinsic P2 promoter, 
resulting in TAp73 and DeltaNup73 isoforms, respectively. The ultimate effect of 
p73 in oncogenesis is thought to depend on the apoptotic TA to antiapoptotic 
DeltaN isoforms' ratio. This study was aimed at identifying novel transcription 
factors that affect TA isoform synthesis. With the use of bioinformatics tools, 
in vitro binding assays, and chromatin immunoprecipitation analysis, a region 
extending -233 to -204 bp upstream of the transcription start site of the human 
p73 P1 promoter, containing conserved Sp1-binding sites, was characterized. 
Treatment of cells with Sp1 RNAi and Sp1 inhibitor functionally suppress TAp73 
expression, indicating positive regulation of P1 by the Sp1 protein. Notably Sp1 
inhibition or knockdown also reduces DeltaNup73 protein levels. Therefore, Sp1 
directly regulates TAp73 transcription and affects DeltaNup73 levels in lung 
cancer. TAp73gamma was shown to be the only TA isoform overexpressed in several 
lung cancer cell lines and in 26 non-small cell lung cancers, consistent with 
Sp1 overexpression, thereby questioning the apoptotic role of this specific p73 
isoform in lung cancer.