Please use this identifier to cite or link to this item: https://doi.org/10.1002/eji.200940034
Title: SARM inhibits both TRIF- and MyD88-mediated AP-1 activation
Authors: Peng, J. 
Yuan, Q. 
Lin, B. 
Panneerselvam, P.
Wang, X. 
Luan, X.L.
Lim, S.K.
Leung, B.P.
Ho, B.
Ding, J.L. 
Keywords: Activator protein 1 inhibition
MAPK
N-terminal polybasic and glycine-rich region motif
Sterile α- and armadillo-motif-containing protein
TLR
Issue Date: Jun-2010
Citation: Peng, J., Yuan, Q., Lin, B., Panneerselvam, P., Wang, X., Luan, X.L., Lim, S.K., Leung, B.P., Ho, B., Ding, J.L. (2010-06). SARM inhibits both TRIF- and MyD88-mediated AP-1 activation. European Journal of Immunology 40 (6) : 1738-1747. ScholarBank@NUS Repository. https://doi.org/10.1002/eji.200940034
Abstract: SARM (sterile α- and armadillo-motif-containing protein), the fifth identified TIR (Toll-interleukin 1 receptor (IL-1R)) domain-containing adaptors in humans, downregulates NF-κB and IRF3 (interferon-regulatory factor 3)-mediated TLR3 and TLR4 signaling. SARM was characterized as a negative regulator of the TRIF (TIR-domain-containing adaptor protein inducing IFN-β)-dependent pathway via its interaction with TRIF. However, the precise mechanism of action of SARM remains unclear. Here, we demonstrate that SARM inhibits MAPK activation in human embryonic kidney 293 cells, and U937 cells. Both the TRIF- and MyD88-mediated, as well as basal MAPK activity, were repressed, indicating that SARM-mediated inhibition may not be exclusively directed at TRIF or MyD88, but that SARM may also directly inhibit MAPK phosphorylation. The MAPK inhibition effect was verified by RNAi, which increased the basal level of AP-1. Furthermore, LPS challenge upregulated SARM at both the mRNA and protein levels. Finally, we provide evidence to show that truncated SARM changes its subcellular localization, suggesting the importance of the N-terminal and sterile alpha motif domains in the autoregulation of SARM activity. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
Source Title: European Journal of Immunology
URI: http://scholarbank.nus.edu.sg/handle/10635/101626
ISSN: 00142980
DOI: 10.1002/eji.200940034
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