| First Author | Ho J | Year | 2016 |
| Journal | PLoS Biol | Volume | 14 |
| Issue | 10 | Pages | e2000117 |
| PubMed ID | 27780205 | Mgi Jnum | J:237351 |
| Mgi Id | MGI:5812605 | Doi | 10.1371/journal.pbio.2000117 |
| Citation | Ho J, et al. (2016) STAT2 Is a Pervasive Cytokine Regulator due to Its Inhibition of STAT1 in Multiple Signaling Pathways. PLoS Biol 14(10):e2000117 |
| abstractText | STAT2 is the quintessential transcription factor for type 1 interferons (IFNs), where it functions as a heterodimer with STAT1. However, the human and murine STAT2-deficient phenotypes suggest important additional and currently unidentified type 1 IFN-independent activities. Here, we show that STAT2 constitutively bound to STAT1, but not STAT3, via a conserved interface. While this interaction was irrelevant for type 1 interferon signaling and STAT1 activation, it precluded the nuclear translocation specifically of STAT1 in response to IFN-gamma, interleukin-6 (IL-6), and IL-27. This is explained by the dimerization between activated STAT1 and unphosphorylated STAT2, whereby the semiphosphorylated dimers adopted a conformation incapable of importin-alpha binding. This, in turn, substantially attenuated cardinal IFN-gamma responses, including MHC expression, senescence, and antiparasitic immunity, and shifted the transcriptional output of IL-27 from STAT1 to STAT3. Our results uncover STAT2 as a pervasive cytokine regulator due to its inhibition of STAT1 in multiple signaling pathways and provide an understanding of the type 1 interferon-independent activities of this protein. |
