| First Author | Becknell B | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 6 | Pages | 2481-7 |
| PubMed ID | 17110450 | Mgi Jnum | J:145357 |
| Mgi Id | MGI:3834342 | Doi | 10.1182/blood-2006-10-050096 |
| Citation | Becknell B, et al. (2007) Hlx homeobox transcription factor negatively regulates interferon-gamma production in monokine-activated natural killer cells. Blood 109(6):2481-7 |
| abstractText | Natural killer (NK) cells contribute to host immunity, including tumor surveillance, through the production of interferon gamma (IFN-gamma). Although there is some knowledge about molecular mechanisms that induce IFN-gamma 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-gamma production by NK cells. Hlx expression is induced in monokine-activated NK cells, but with delayed kinetics compared to IFN-gamma. Ectopic Hlx expression decreases IFN-gamma synthesis in primary human NK cells and IFN-gamma promoter activity in an NK-like cell line. Hlx protein levels inversely correlate with those of STAT4, a requisite factor for optimal IFN-gamma 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-gamma, in part through the targeted depletion of STAT4. |
