Nuclear dot protein 52, an autophagy-associated protein, regulates Toll-like receptor signaling

Publication date: August 2012 Source:Journal of Oral Biosciences, Volume 54, Issue 3 Author(s): Megumi Inomata , Takeshi Into Toll-like receptors (TLRs) recognize molecular patterns on various microbes and serve as innate immune sensors. After cognate ligand recognition, TLRs activate signaling pathways to induce innate immune defense mechanisms, which eliminate pathogenic microbes, including periodontogenic bacteria, to a certain extent. Recent findings have shown that TLR signaling is linked to induction of autophagy to facilitate direct killing of cytosol-invading bacteria within infected cells. However, whether autophagy has any regulatory effects on TLR signaling remains unclear. Our recent study showed that the signaling molecules Toll/interleukin-1 receptor homology domain-containing adaptor inducing interferon-β and tumor necrosis factor receptor-associated factor 6 are selectively degraded by autophagy after activation of TLR signal transduction. We found that the nuclear dot protein 52 (NDP52), an autophagy-associated protein, is involved in such degradation, negatively regulating TLR signaling. However, interestingly, this activity of NDP52 is strictly restricted by the deubiquitinase A20. Here, we describe an autophagy-associated regulatory function of NDP52 in TLR signaling on the basis of our recent findings.
Source: Journal of Oral Biosciences - Category: Biomedical Science Source Type: research