title: MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity.
abstract: Identification of cytokine-inducible genes is imperative for determining the mechanisms of cytokine action. A cytokine-inducible gene, mrg1 [melanocyte-specific gene (msg1) related gene], was identified through mRNA differential display of interleukin (IL) 9-stimulated and unstimulated mouse helper T cells. In addition to IL-9, mrg1 can be induced by other cytokines and biological stimuli, including IL-1alpha, -2, -4, -6, and -11, granulocyte/macrophage colony-stimulating factor, interferon gamma, platelet-derived growth factor, insulin, serum, and lipopolysaccharide in diverse cell types. The induction of mrg1 by these stimuli appears to be transient, with induction kinetics similar to other primary response genes, implicating its role in diverse biological processes. Deletion or point mutations of either the Box1 motif (binds Janus kinase 1) or the signal transducer and activator of transcription 3 binding site-containing region within the intracellular domain of the IL-9 receptor ligand binding subunit abolished or greatly reduced mrg1 induction by IL-9, suggesting that the Janus kinase/signal transducer and activator of transcription signaling pathway is required for mrg1 induction, at least in response to IL-9. Transfection of mrg1 cDNA into TS1, an IL-9-dependent mouse T cell line, converted these cells to IL-9-independent growth through a nonautocrine mechanism. Overexpression of mrg1 in Rat1 cells resulted in loss of cell contact inhibition, anchorage-independent growth in soft agar, and tumor formation in nude mice, demonstrating that mrg1 is a transforming gene. MRG1 is a transcriptional activator and may represent a founding member of an additional family of transcription factors.
authors.affiliation: Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, and Walther Cancer Institute, 1044 West Walnut Street, R4-272, Indianapolis, IN 46202, USA.
authors.forename: H B
authors.initials: HB
authors.lastname: Sun
authors.forename: Y X
authors.initials: YX
authors.lastname: Zhu
authors.forename: T
authors.initials: T
authors.lastname: Yin
authors.forename: G
authors.initials: G
authors.lastname: Sledge
authors.forename: Y C
authors.initials: YC
authors.lastname: Yang
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D012097:Repressor Proteins; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C110087:Cited2 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors