Overproduced p73α activates a minimal promoter through a mechanism independent of its transcriptional activity

p73, the gene for a protein related to the tumor suppressor p53, encodes several variants which bear distinct carboxy-terminal structures as a result of alternative splicing. We and others showed that these splicing variants have different transcriptional effects on promoters with a p53-binding consensus sequence (p53BCS). Here we show that when transiently overexpressed, p73 alpha but not p73 beta activated several minimal promoters without the p53BCS, while p73 gamma and p73 epsilon activated them to a much lesser extent than p73 alpha, and p53 suppressed the promoters without p53BCS as reported previously. Moreover, the results of RNase protection and RNA transfection assays suggested that this activation occurred at the transcriptional level. Deletion analysis of p73 alpha revealed that the transactivation domain of p73 was not involved in this activity and the C-terminal region of p73 alpha which is a specific structure of this variant was essential, suggesting that this phenomenon occurs independent of the transactivation activity of p73 alpha and that the C-terminal extension of p73 alpha may affect the basal level of transcription. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.