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Inactivation of p53 is one of the most relevant events in human cancer, since it allows transformed cells to escape their own proliferation control and leave them irresponsive to drugs that aim to damage their DNA. When p53 falls, other members of its family may become targets to attack tumoral cells. p73 has shown capacity to mediate these attacks. However, its N-terminal truncated isoforms have been associated with oncogenesis due to their capacity to act as dominant negatives of p53 and the TA isoforms of p73. We previously found a relationship between the overexpression of ΔNp73 and that of the proapoptotic gene BIK. In the present report we demonstrate that ΔNp73 α has the capacity to induce apoptosis through the coordinated activation of a group of genes harboring GC-rich elements in their regulatory regions. ΔNp73 α synergizes with Sp1 on these elements but the overall response of these genes probably depends on the additional presence of consensus p53 elements. We explore the domains of ΔNp73 α involved in this transactivation capacity and found divergences with the previously described functions for them. Moreover, we found that the transforming mutation V12 of HRas impairs this transactivation capacity of ΔNp73 α, further supporting the antitumoral function of this later. Our data add complexity to the action of p73 on the induction of apoptosis and tumorogenesis, opening new interpretations to the expression profile of p73 isoforms in different human neoplasias. [ABSTRACT FROM AUTHOR]