Stable Identifier
Reaction [binding]
Homo sapiens
Negative regulator SARM binds to TRIF within activated TLR4 complex
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SARM (sterile alpha-and armadillo-motif-containing protein) is a TIR-domain-containing adaptor, which functions as a negative regulator of TRIF (TICAM1)-dependent Toll-like receptor signaling in humans. A pairwise yeast two-hybrid assay demonstrated that SARM is capable of binding directly to TICAM1 (Carty M et al. 2006). GST pulldown studies suggest that protein-protein interactions occur between the TIR domains of SARM and TICAM1 (Carlsson E et al. 2016). The complex of TICAM1:SARM is thought to inhibit downstream TRIF signaling by preventing the recruitment of TRIF effector proteins (Carty M et al. 2006).

LPS treatment led to a rapid increase of the SARM expression in peripheral blood mononuclear cells (PBMCs) and as a result an increased association between SARM and TICAM1 (Carty M et al. 2006). Moreover, suppression of endogenous SARM expression by siRNA led to enhanced TLR4-dependent gene induction in both transformed HEK293 and primary PBMC cells, while endotoxin-tolerant human monocytes showed increased expression of SARM and decreased activation of TICAM1-dependent cytokines (Carty M et al. 2006; Piao W et al. 2009). Thus, SARM negatively regulates TICAM1 (TRIF)-dependent TLR4 signaling pathway.

Literature References
PubMed ID Title Journal Year
19656901 Endotoxin tolerance dysregulates MyD88- and Toll/IL-1R domain-containing adapter inducing IFN-beta-dependent pathways and increases expression of negative regulators of TLR signaling

Chen, H, Piao, W, Fitzgerald, KA, Li, L, Diaz, MA, Medvedev, AE, Wahl, LM, Song, C

J. Leukoc. Biol. 2009
16964262 The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling

Schröder, M, Stack, J, Moynagh, PN, Carty, M, Bowie, AG, Goodbody, R

Nat. Immunol. 2006
Event Information
Orthologous Events
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