Hlx homeobox transcription factor negatively regulates interferon-production in monokine-activated natural killer cells

activated NK cells, but with delayed kinet- ics compared to IFN-. Ectopic Hlx expres- sion decreases IFN-synthesis in primary human NK cells and IFN- promoter activ- ity in an NK-like cell line. Hlx protein levels inversely correlate with those of STAT4, a requisite factor for optimal IFN- transcription. Mechanistically, we pro- vide evidence indicating that Hlx overex- pression accelerates dephosphorylation and proteasome-dependent degradation of the active Y693-phosphorylated form of STAT4. Thus, Hlx expression in acti- vated NK cells temporally controls and limits the monokine-induced produc- tion of IFN-, in part through the tar- geted depletion of STAT4. (Blood. 2007; 109:2481-2487)