title: NAB2 and EGR-1 exert opposite roles in regulating TRAIL expression in human Natural Killer cells.
abstract: The transcriptional regulator NGFI-A binding protein 2 (NAB2) and the early growth response (EGR) genes are key regulators of effector molecules, such as cell death-inducing genes. We have previously shown that NAB2 modulates the levels of expression of the Tumor Necrosis Factor (TNF) family member TNF-related apoptosis inducing ligand (TRAIL) in T cells and plasmacytoid DCs. Provided that TRAIL plays a key role in NK cell cytotoxicity towards infected and tumor cells, we investigated whether NAB2 also mediates TRAIL expression in human NK cells, and if so through which mechanisms. We show that NAB2 is induced in NK cells upon IL-2 and IL-15 stimulation, and promotes the induction of TRAIL. In addition, we show that the transcription factor EGR-1, which is upregulated by the same stimuli as NAB2, rather acts as a brake on TRAIL expression in NK cells. Overall, these data provide new mechanistic insights in the regulation of TRAIL, and show that the gene regulation through the NAB2/EGR axis allows for a highly controlled expression pattern of this effector molecule in NK cells.
authors: Laboratory of Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine (CEMM), Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
authors: Melania
authors: M
authors: Balzarolo
authors: Carsten
authors: C
authors: Watzl
authors: Jan Paul
authors: JP
authors: Medema
authors: Monika C
authors: MC
authors: Wolkers
mesh_terms: D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism
chemical_list: D051766:Early Growth Response Protein 1; D019409:Interleukin-15; C491000:NAB2 protein, human; D012097:Repressor Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D018664:Interleukin-12