| First Author | Sanada T | Year | 2008 |
| Journal | J Biol Chem | Volume | 283 |
| Issue | 49 | Pages | 33858-64 |
| PubMed ID | 18849341 | Mgi Jnum | J:144594 |
| Mgi Id | MGI:3831253 | Doi | 10.1074/jbc.M806923200 |
| Citation | Sanada T, et al. (2008) FLN29 deficiency reveals its negative regulatory role in the Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like helicase signaling pathway. J Biol Chem 283(49):33858-64 |
| abstractText | FLN29 was identified as an interferon (IFN)-inducible gene, and it has been shown to suppress Toll-like receptor 4-mediated NF-kappaB activation by binding to TRAF6. To elucidate the physiological roles of FLN29, we generated FLN29-deficient mice. FLN29 deficiency resulted in hyper-response to LPS both in vivo and in vitro, demonstrating the negative regulatory role of FLN29 in TLR4 signaling. Furthermore, we found that FLN29(-/-) mice exhibited increased susceptibility to poly(I:C)-induced septic shock compared with WT mice. FLN29(-/-) fibroblasts were highly resistant to vesicular stomatitis virus infection, and these cells produced more IFN-beta than WT cells did in response to not only intracellular poly(I:C) but also overexpression of IPS-1. Forced expression of FLN29 inhibited the IPS-1-dependent activation of both NF-kappaB and IRF3. We also found that FLN29 could interact with TRIF, IPS-1, TRAF3, and TRAF6. Together, these results suggest that FLN29, in addition to playing a negative regulatory role in the TLR4 signaling pathway, negatively regulates the RIG-I-like helicase signaling pathway at the level of IPS-1/TRAF6 and IPS-1/TRAF3 complexes. |
