TOLLIP gene

The TOLLIP gene (TOLLIP stands for Toll Interacting Protein) is a protein-coding gene located on chromosome 11p15.5. The TOLLIP gene encodes a ubiquitin-binding protein that interacts with several components of the Toll-like receptor (TLR) signaling cascade. The encoded protein regulates inflammatory signaling and is involved in interleukin-1 receptor trafficking and IL1R-associated kinase turnover. Several transcript variants encoding different isoforms have been found for this gene.

Diseases associated with TOLLIP include tick paralysis and acute intestinal vascular insufficiency.

Related signaling pathways include innate immune system and bacterial infections in the CF airways.

Component of the IL-1 and Toll-like receptor signaling pathway (Burns K et al. 2000).

Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex (Burns K et al. 2000). Inhibits the phosphorylation and kinase activity of IRAK1 (Lu K et al. 2014). Links the ubiquitin pathway to autophagy by acting as an adaptor of the ubiquitin-ATG8 family, mediating autophagic clearance of ubiquitin conjugates . The TOLLIP-dependent selective autophagy pathway plays an important role in the clearance of cytotoxic polyQ protein aggregates (Lu K et al. 2014). Recruited in a complex with TOM1 ubiquitin conjugates.

1. Burns K et al. (2000) Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nat Cell Biol 2:346-351.
2. Lu K et al. (2014) Autophagic clearance of polyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family. Cell 158:549-563.
3. Zhang G et al. (2002) Negative regulation of toll-like receptor-mediated signaling by Tollip. J Biol Chem 277:7059-7065.