Activation of protein phosphatase-1 as a novel cancer therapy.

Small-molecule inhibitors of protein kinases are now widely and successfully used for the treatment of various cancers. Since an activator of a counteracting phosphatase is functionally equivalent to a kinase inhibitor, we propose to explore the therapeutic potential of activating PP1, a major protein Ser/Thr phosphatase. More specifically, we will investigate whether the constitutive activation of PP1-NIPP1, a PP1 holoenzyme that we recently identified as a tumor suppressor in liver, can be used for a cancer-cell differentiation therapy. In addition, we will examine whether our recently developed cell-permeable peptide APP1, which generates an active pool of intracellular PP1 and causes the precocious dephosphorylation of mitotic substrates, can be used to specifically kill cancer cells, either alone or as a sensitizer for clinically used kinase inhibitors.

Keywords:Cancer cell differentiation therapy, Tumor suppressor NIPP1, Protein kinase inhibitor, Protein phosphatase 1 activator

Disciplines:Morphological sciences, Oncology