Functional proteomic analysis reveals roles for PKCδ in regulation of cell survival and cell death: Implications for cancer pathogenesis and therapy.

Protein Kinase C-δ (PKCδ), regulates a broad group of biological functions and disease processes, including well-defined roles in immune function, cell survival and apoptosis. PKCδ primarily regulates apoptosis in normal tissues and non-transformed cells, and genetic disruption of the PRKCD gene in mice is protective in many diseases and tissue damage models. However pro-survival/pro-proliferative functions have also been described in some transformed cells and in mouse models of cancer. Recent evidence suggests that the contribution of PKCδ to specific cancers may depend in part on the oncogenic context of the tumor, consistent with its paradoxical role in cell survival and cell death. Here we will discuss what is currently known about biological functions of PKCδ and potential paradigms for PKCδ function in cancer. To further understand mechanisms of regulation by PKCδ, and to gain insight into the plasticity of PKCδ signaling, we have used functional proteomics to identify pathways that are dependent on PKCδ. Understanding how these distinct functions of PKCδ are regulated will be critical for the logical design of therapeutics to target this pathway.