Functional cross-talk between p73β and NF-κB mediated by p300

p73β is associated with induction of apoptosis or cellular growth arrest, while NF-κB is closely related with promotion of resistance to programmed cell death. These biologically opposing activities between p73β and NF-κB propose a regulatory mechanism of critical turning on/off in cellular apoptotic or survival responses. In this study, we demonstrate that NF-κB-mediated transactivation is specifically downregulated by p73β; conversely, p73β-transactivation is negatively regulated by functional expression of p65, NF-κB RelA subunit. The p73β transactivation domain (TA) and p65 NH2-terminus are crucial for their negative regulation of p65- and p73β-mediated transactivation, respectively. Furthermore, p65- or p73β-interaction with p300 is reciprocally inhibited by their competitive binding to p300 in a restrict amount-dependent manner. Likewise, both p73β-activated apoptosis and p65-dependent increase of cell viability are reciprocally repressed by p65 and p73β, respectively. These results have important implications for p300-mediated regulatory mechanism between p73β- and p65-transactivation, by which both p73β and NF-κB could mutually affect on their biological activities. Therefore, we propose that p300 is a transactivational regulator of competitively balanced cross-talk between p73β and p65.