"Convergence of Protein Kinase and Caspase Pathways: A Mechanism for Pathological Rewiring of Survival Pathways by an Oncogenic Protein Kinase?"

A central goal of our research is to understand how protein kinases that are aberrantly expressed in malignancy promote cancer cell survival. One intriguing mechanism where protein kinases have been implicated in the control of cell survival is through the phosphorylation of caspase substrates to modulate cleavage and the progression of apoptosis. To examine the convergence between protein kinase and caspase pathways, we devised systematic computational and proteomic strategies to identify proteins with kinase recognition motifs that overlap with caspase cleavage sites. These studies revealed a broad repertoire of proteins with overlapping kinase and caspase recognition sites suggesting that phosphorylation may have widespread impact on caspase action. Notably, protein kinase CK2, a small family of kinases implicated in a number of malignancies emerged with the most prominent overlap with caspase recognition motifs. Given that CK2 is constitutively active, our studies raise the prospect that its elevated kinase activity that accompanies many forms of cancer can lead to a pathological rewiring of apoptotic pathways to promote cell survival and tumorigenesis.