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These ligands are recognized by activating receptors on <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells, such as <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2D. In addition to activation by cell surface ligands, the acquisition of optimal effector activity by <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells is driven in vivo by cytokines and other signals. This review addresses a developing theme in <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cell biology: that <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>\u2010activating ligands on cells, and the provision of cytokines and other signals that drive high effector function in <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells, are driven by abnormalities that arise from transformation or the infected state. The pathways include genomic damage, which causes self <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> to be exposed in the cytosol of affected cells, where it activates the <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sensor <jats:styled-content style=\"fixed-case\">cGAS<\/jats:styled-content>. The resulting signaling induces <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2D ligands and also mobilizes <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cell activation. Other key pathways that regulate <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2D ligands include <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\u20103 kinase activation, histone acetylation, and the integrated stress response. This review summarizes the roles of these pathways and their relevance in both viral infections and cancer.<\/jats:p>","DOI":"10.1111\/imr.12600","type":"journal-article","created":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T06:55:18Z","timestamp":1507877718000},"page":"93-101","source":"Crossref","is-referenced-by-count":64,"title":["Dysregulated cellular functions and cell stress pathways provide critical cues for activating and targeting natural killer cells to transformed and infected cells"],"prefix":"10.1111","volume":"280","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-8649","authenticated-orcid":false,"given":"David H.","family":"Raulet","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology Cancer Research Laboratory, Immunotherapy and Vaccine Research Initiative University of California, Berkeley  Berkeley CA 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