Publication Date:
2014-05-21
Description:
The transcription factor STAT1 is essential for interferon (IFN)-mediated immunity in humans and mice. STAT1 function is tightly regulated, and both loss- and gain-of-function mutations result in severe immune diseases. The two alternatively spliced isoforms, STAT1α and STAT1β, differ with regard to a C-terminal transactivation domain, which is absent in STAT1β. STAT1β is considered to be transcriptionally inactive and to be a competitive inhibitor of STAT1α. To investigate the functions of the STAT1 isoforms in vivo , we generated mice deficient for either STAT1α or STAT1β. As expected, the functions of STAT1α and STAT1β in IFN-α/β- and IFN--dependent antiviral activity are largely redundant. In contrast to the current dogma, however, we found that STAT1β is transcriptionally active in response to IFN-. In the absence of STAT1α, STAT1β shows more prolonged IFN--induced phosphorylation and promoter binding. Both isoforms mediate protective, IFN--dependent immunity against the bacterium Listeria monocytogenes , although with remarkably different efficiencies. Our data shed new light on the potential contributions of the individual STAT1 isoforms to STAT1-dependent immune responses. Knowledge of STAT1β's function will help fine-tune diagnostic approaches and help design more specific strategies to interfere with STAT1 activity.
Print ISSN:
0270-7306
Electronic ISSN:
1098-5549
Topics:
Biology
,
Medicine
Permalink