| First Author | Semper C | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 12 | Pages | 2235-48 |
| PubMed ID | 24710278 | Mgi Jnum | J:221627 |
| Mgi Id | MGI:5641149 | Doi | 10.1128/MCB.00295-14 |
| Citation | Semper C, et al. (2014) STAT1beta is not dominant negative and is capable of contributing to gamma interferon-dependent innate immunity. Mol Cell Biol 34(12):2235-48 |
| abstractText | 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, STAT1alpha and STAT1beta, differ with regard to a C-terminal transactivation domain, which is absent in STAT1beta. STAT1beta is considered to be transcriptionally inactive and to be a competitive inhibitor of STAT1alpha. To investigate the functions of the STAT1 isoforms in vivo, we generated mice deficient for either STAT1alpha or STAT1beta. As expected, the functions of STAT1alpha and STAT1beta in IFN-alpha/beta- and IFN-lambda-dependent antiviral activity are largely redundant. In contrast to the current dogma, however, we found that STAT1beta is transcriptionally active in response to IFN-gamma. In the absence of STAT1alpha, STAT1beta shows more prolonged IFN-gamma-induced phosphorylation and promoter binding. Both isoforms mediate protective, IFN-gamma-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 STAT1beta's function will help fine-tune diagnostic approaches and help design more specific strategies to interfere with STAT1 activity. |
