| First Author | Biswas N | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 6 | Pages | e21153 |
| PubMed ID | 21695056 | Mgi Jnum | J:219184 |
| Mgi Id | MGI:5619743 | Doi | 10.1371/journal.pone.0021153 |
| Citation | Biswas N, et al. (2011) The ubiquitin-like protein PLIC-1 or ubiquilin 1 inhibits TLR3-Trif signaling. PLoS One 6(6):e21153 |
| abstractText | BACKGROUND: The innate immune responses to virus infection are initiated by either Toll-like receptors (TLR3/7/8/9) or cytoplasmic double-stranded RNA (dsRNA)-recognizing RNA helicases RIG-I and MDA5. To avoid causing injury to the host, these signaling pathways must be switched off in time by negative regulators. METHODOLOGY/PRINCIPAL FINDINGS: Through yeast-two hybrid screening, we found that an ubiquitin-like protein named protein linking integrin-associated protein to cytoskeleton 1(PLIC-1 or Ubiquilin 1) interacted with the Toll/interleukin-1 receptor (TIR) domain of TLR4. Interestingly, PLIC-1 had modest effect on TLR4-mediated signaling, but strongly suppressed the transcriptional activation of IFN-beta promoter through the TLR3-Trif-dependent pathway. Concomitantly, reduction of endogenous PLIC-1 by short-hairpin interfering RNA (shRNA) enhanced TLR3 activation both in luciferase reporter assays as well as in new castle disease virus (NDV) infected cells. An interaction between PLIC-1 and Trif was confirmed in co-immunoprecipitation (Co-IP) and GST-pull-down assays. Subsequent confocal microscopic analysis revealed that PLIC-1 and Trif colocalized with the autophagosome marker LC3 in punctate subcellular structures. Finally, overexpression of PLIC-1 decreased Trif protein abundance in a Nocodazole-sensitive manner. CONCLUSIONS: Our results suggest that PLIC-1 is a novel inhibitor of the TLR3-Trif antiviral pathway by reducing the abundance of Trif. |
