TY - JOUR
T1 - The E3-Ligase TRIM Family of Proteins Regulates Signaling Pathways Triggered by Innate Immune Pattern-Recognition Receptors
AU - Versteeg, Gijs A.
AU - Rajsbaum, Ricardo
AU - Sánchez-Aparicio, Maria Teresa
AU - Maestre, Ana M.
AU - Valdiviezo, Julio
AU - Shi, Mude
AU - Inn, Kyung Soo
AU - Fernandez-Sesma, Ana
AU - Jung, Jae
AU - García-Sastre, Adolfo
N1 - Funding Information:
This research is partially supported by NIAID grants U54 AI57158 (North East Biodefense Center) (to A.G.-S.), R01DA033733 (to A.G.-S.), U19AI83025, (to A.G.-S. and J.J.), and P01AI090935 (to A.G.-S. and A.F.-S.). We thank J. Ayllon for kindly providing the ISG54 ISRE-luciferase reporter plasmid and D. Littman for providing plasmid pSIV3+. We thank A. Ballabio, P. Bieniasz, and F. Naya for kindly providing the TRIM expression plasmids specified in the supplemental information. We are grateful to M. Ooms for technical assistance related to lentivirus production and to R. Cadagan and O. Lizardo for technical support.
PY - 2013/2/21
Y1 - 2013/2/21
N2 - Innate immunity conferred by the type I interferon is critical for antiviral defense. To date only a limited number of tripartite motif (TRIM) proteins have been implicated in modulation of innate immunity and anti-microbial activity. Here we report the complementary DNA cloning and systematic analysis of all known 75 human TRIMs. We demonstrate that roughly half of the 75 TRIM-family members enhanced the innate immune response and that they do this at multiple levels in signaling pathways. Moreover, messenger RNA levels and localization of most of these TRIMs were found to be altered during viral infection, suggesting that their regulatory activities are highly controlled at both pre- and posttranscriptional levels. Taken together, our data demonstrate a very considerable dedication of this large protein family to the positive regulation of the antiviral response, which supports the notion that this family of proteins evolved as a component of innate immunity.
AB - Innate immunity conferred by the type I interferon is critical for antiviral defense. To date only a limited number of tripartite motif (TRIM) proteins have been implicated in modulation of innate immunity and anti-microbial activity. Here we report the complementary DNA cloning and systematic analysis of all known 75 human TRIMs. We demonstrate that roughly half of the 75 TRIM-family members enhanced the innate immune response and that they do this at multiple levels in signaling pathways. Moreover, messenger RNA levels and localization of most of these TRIMs were found to be altered during viral infection, suggesting that their regulatory activities are highly controlled at both pre- and posttranscriptional levels. Taken together, our data demonstrate a very considerable dedication of this large protein family to the positive regulation of the antiviral response, which supports the notion that this family of proteins evolved as a component of innate immunity.
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U2 - 10.1016/j.immuni.2012.11.013
DO - 10.1016/j.immuni.2012.11.013
M3 - Article
C2 - 23438823
AN - SCOPUS:84874256730
SN - 1074-7613
VL - 38
SP - 384
EP - 398
JO - Immunity
JF - Immunity
IS - 2
ER -