title: Noncanonical IFN Signaling: Mechanistic Linkage of Genetic and Epigenetic Events.
abstract: The canonical model of cytokine signaling via the JAK/STAT pathway dominates our view of signal transduction but provides no insight into the significance of the simultaneous presence of activated JAKs and STATs in the nucleus of cells treated with cytokines. Such a mechanistic shortcoming challenges the usefulness of the model in its present form. Focusing on the interferon (IFN) cytokines, we have developed a noncanonical model of IFN signaling that naturally connects activated JAKs and STATs at or near response elements of genes that are activated by the IFNs. Specifically, cells treated with IFNγshowed association of activated STAT1αand JAK2 at the GAS element of genes activated by IFNγ. For IFNαtreated cells, the association involved activated STAT1αand TYK2 JAK kinase at the ISRE promoter. The power of the noncanonical model is that it provides mechanistic insight into specific gene activation at the level of the associated epigenetics, akin to that of steroid/steroid receptor signaling.
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611-0700, USA.
authors.forename: Howard M
authors.identifier: 0000-0003-2706-1623
authors.initials: HM
authors.lastname: Johnson
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611-0700, USA.
authors.forename: Chulbul M
authors.initials: CM
authors.lastname: Ahmed
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D044127:Epigenesis, Genetic; D066246:ErbB Receptors / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000235:genetics; D053612:Janus Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017467:Receptors, Erythropoietin / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017467:Receptors, Erythropoietin; D050791:STAT Transcription Factors; D007372:Interferons; D066246:ErbB Receptors; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D053612:Janus Kinases