|
|
Blood, 15 March 2007, Vol. 109, No. 6, pp. 2481-2487.
Prepublished online as a Blood First Edition Paper on December 14, 2006; DOI 10.1182/blood-2006-10-050096.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
Hlx homeobox transcription factor negatively regulates interferon- production in monokine-activated natural killer cells
Brian Becknell1,2,
Tiffany L. Hughes2,
Aharon G. Freud1,2,
Bradley W. Blaser1,2,
Jianhua Yu3,
Rossana Trotta3,
Hsiaoyin C. Mao3,
Marie L. Caligiuri de Jesús4,
Mohamad Alghothani4,
Don M. Benson, Jr4,
Amy Lehman5,
David Jarjoura5,
Danilo Perrotti6,8,
Michael D. Bates7, and
Michael A. Caligiuri2,4,8
1 Medical Scientist Program,
2 Integrated Biomedical Science Graduate Program,
3 Department of Molecular Virology, Immunology, and Medical Genetics,
4 Division of Hematology/Oncology,
5 Department of Epidemiology and Biometrics,
6 Human Cancer Genetics Program, Department of Internal Medicine, College of Medicine and Public Health, The Ohio State University, Columbus;
7 Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, OH;
8 Comprehensive Cancer Center, The Ohio State University, Columbus
Natural killer (NK) cells contribute to host immunity, including tumor surveillance, through the production of interferon gamma (IFN- ). Although there is some knowledge about molecular mechanisms that induce IFN- in NK cells, considerably less is known about the mechanisms that reduce its expression. Here, 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 and 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 overexpression accelerates dephosphorylation and proteasome-dependent degradation of the active Y693-phosphorylated form of STAT4. Thus, Hlx expression 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]
|
|
|
| |
