Figure 3.

PKC regulation of nuclear function in the control of proliferation and apoptosis. PKC isozymes exert proliferative/prosurvival and antiproliferative/apoptotic roles in distinct cell contexts. A, the dual roles of PKC isozymes in proliferation are indicative of either positive (upper panel) or negative (lower panel) control of the cell cycle, acting in different phases with characteristic isozyme and cell type specificity. B, representative examples for positive (upper panels) and negative (lower panels) controls of nuclear events by PKC isozymes. The lower panel also includes an established paradigm for PKCδ in apoptotic signaling in response to chemotherapeutic drugs and irradiation. These stimuli promote PKCδ phosphorylation by soluble tyrosine kinases (STKs), exposure of a cryptic NLS, binding to importin, cytoplasmatic-nuclear shuttling, and nuclear cleavage by caspase-3, leading to the generation of an active PKCδ catalytic fragment (δ-CAT). NLS, nuclear localization signal.