Protein Kinase R as Mediator of the Effects of Interferon (IFN) γ and Tumor Necrosis Factor (TNF) α on Normal and Dysplastic Hematopoiesis

• DOI: 10.1074/jbc.m111.238501
• Publication Date: 2011-06-10T08:22:44Z
• Authors: Bhumika Sharma; Jessica K. Altman; Dennis J. Goussetis; Amit K. Verma; Leonidas C. Plata...
• Keywords: Protein kinase R

IFNγ and TNFα are potent inhibitors of hematopoiesis have been implicated in the pathophysiology bone marrow failure myelodysplastic syndromes (MDS). We examined role protein kinase R (PKR) generation inhibitory effects these myelosuppressive cytokines on hematopoiesis. Our data demonstrate that PKR is rapidly phosphorylated/activated response to engagement or receptors normal human hematopoietic progenitors. Such important for suppressive Pharmacological targeting using a specific inhibitor siRNA-mediated knockdown results partial reversal CD34+-derived myeloid (colony-forming unit-granulocyte-monocytic) erythroid (burst-forming unit-erythroid) Importantly, inhibition activity expression increases colony formation from MDS progenitors, suggesting drugs target may provide novel approach treatment syndromes. Altogether, our establish beyond its key induction IFN-antiviral responses, plays roles signaling other cytokine as common mediator signals suppression.