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.
Carty, M, Goodbody, R, Schröder, M, Stack, J, Moynagh, PN, Bowie, AG
Piao, W, Song, C, Chen, H, Diaz, MA, Wahl, LM, Fitzgerald, KA, Li, L, Medvedev, AE
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