TAp73alpha protects small cell lung carcinoma cells from caspase-2 induced mitochondrial mediated apoptotic cell death

Naveen Muppani 1 , Ulrika Nyman 1,2 , and Bertrand Joseph 1 1 Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, 171 76 Stockholm, Sweden 2 Present address: Ludwig Institute for Cancer Research, 171 77 Stockholm, Sweden Received: December 19, 2011; Accepted: December 21, 2011; Published: December 22, 2011; Keywords: p73, caspase-2, apoptosis, cancer Correspondence: Ulrika Nyman, email: // // Abstract Caspase-2 is ubiquitously expressed and the most evolutionarily conserved mammalian caspase. It can be activated by a range of death stimuli prior to Bax activation and the occurrence of apoptotic mitochondrial dysfunctions. Caspase-2 has also been reported to exert tumour suppressor function in vivo . The full length TAp73alpha isoform is found up-regulated in various tumour types, and is reported in a cell-type specific manner to repress drug-induced apoptosis. Here, we report that TAp73alpha represses caspase-2 enzymatic activity and by this means reduce caspase-2 induced Bax activation, loss of mitochondrial transmembrane potential and resulting apoptosis. The inhibitory effect on caspase-2 requires the presence of the DNA binding domain and SAM domain region of TAp73alpha. In conclusion, the ability of TAp73alpha to act as an inhibitor of caspase-2-induced cell death together with its up-regulation in certain tumour types strengthen the potential oncogenic activities for this protein.