Abstract 51: Nucleostemin Induced by Pim-1 Kinase Is Critical to Maintain Pluripotency and Enhance Regenerative Potential of Cardiac Progenitor Cells

Myocardial regeneration and repair in response to injury are governed in part by cell survival, proliferation and pluripotency. Proliferation and survival in cardiac progenitor cells (CPCs) are mediated by Pim-1, a serine threonine kinase, and nucleostemin (NS), a nucleolar stress sensor protein. The role of NS in regulating CPC pluripotency and the molecular mechanism of NS induction and action is largely unknown. The hypothesis of the study is that NS, induced by Pim-1 mediated stabilization of transcription factor c-Myc is critical to maintain CPC pluripotency and inhibits senescence. NS and c-Myc protein levels are increased in cultured CPCs overexpressing Pim-1 (3.1 and 5.5 fold, p<0.01) while knockdown of Pim-1 using sh-RNA decreases c-Myc and NS expression (-60%, -54%, p<0.05), similar to effects mediated by a Pim-1 kinase inhibitor (p<0.01), indicating that Pim-1 regulates both c-Myc and NS. c-Myc is necessary and sufficient for NS regulation, as indicated by the increase (3.1 fold, p<0.01) and de...