SEARCH:   Advanced

Blood, 15 March 2007, Vol. 109, No. 6, pp. 2481-2487. Prepublished online as a Blood First Edition Paper on December 12, 2006December 14, 2006; DOI 10.1182/blood-2006-10-050096. This Article Full Text (PDF) All Versions of this Article: blood-2006-10-050096v1 blood-2006-10-050096v2 blood-2006-10-050096v3 109/6/2481    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Becknell, B. Articles by Caligiuri, M. A. Search for Related Content PubMed PubMed Citation Articles by Becknell, B. Articles by Caligiuri, M. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 10, 2006 Accepted November 6, 2006 The Hlx homeobox transcription factor negatively regulates interferon- production in monokine-activated natural killer cells Brian Becknell, Tiffany L. Hughes, Aharon G. Freud, Bradley W. Blaser, Jianhua Yu, Rossana Trotta, Hsiaoyin C. Mao, Marie L. Caligiuri de Jesus, Mohamad Alghothani, Don M. Benson Jr., Amy Lehman, David Jarjoura, Danilo Perrotti, Michael D. Bates, and Michael A. Caligiuri* Medical Scientist Program, The Ohio State University, Columbus, OH, United States Integrated Biomedical Science Graduate Program, The Ohio State University, Columbus, OH, United States Dept of Molecular Virology, Immunology & Medical Genetics, The Ohio State University, Columbus, OH, United States Division of Hematology/Oncology, The Ohio State University, Columbus, OH, United States Dept of Epidemiology & Biometrics, The Ohio State University, Columbus, OH, United States Human Cancer Genetics Program, Dept of Internal Medicine, College of Medicine & Public Health, The Ohio State University, Columbus, OH, United States Division of Gastroenterology, Hepatology & Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati College of Medicine, Cincinnati, OH, United States The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States * Corresponding author; email: michael.caligiuri{at}osumc.edu. Natural killer (NK) cells contribute to host immunity including tumor surveillance through the production of interferon gamma (IFN-). While there is some knowledge about molecular mechanisms that induce IFN- in NK cells, considerably less is known of the mechanisms that reduce its expression. Herein, we investigate the role of the Hlx transcription factor in IFN- production by NK cells. Hlx expression is induced in monokine-activated NK cells, but with delayed kinetics compared to IFN-. Ectopic Hlx expression decreases IFN- synthesis in primary human NK cells as well as IFN- promoter activity in an NK-like cell line. Hlx protein levels inversely correlate with those of STAT4, a requisite factor for optimal IFN- transcription. Mechanistically, we provide evidence indicating that Hlx over-expression accelerates dephosphorylation and proteasome-dependent degradation of the active Y693-phosphorylated form of STAT4. Thus, expression of Hlx in activated NK cells temporally controls and limits the monokine-induced production of IFN- in part through the targeted depletion of STAT4. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. M. Rosenberger, A. E. Clark, P. M. Treuting, C. D. Johnson, and A. Aderem ATF3 regulates MCMV infection in mice by modulating IFN-{gamma} expression in natural killer cells PNAS, February 19, 2008; 105(7): 2544 - 2549. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020