Mapping a Dynamic Innate Immunity Protein Interaction Network Regulating Type I Interferon Production

78Citations
Citations of this article
268Readers
Mendeley users who have this article in their library.

Abstract

To systematically investigate innate immune signaling networks regulating production of type I interferon, we analyzed protein complexes formed after microbial recognition. Fifty-eight baits were associated with 260 interacting proteins forming a human innate immunity interactome for type I interferon (HI5) of 401 unique interactions; 21% of interactions were modulated by RNA, DNA, or LPS. Overexpression and depletion analyses identified 22 unique genes that regulated NF-κB and ISRE reporter activity, viral replication, or virus-induced interferon production. Detailed mechanistic analysis defined a role for mind bomb (MIB) E3 ligases in K63-linked ubiquitination of TBK1, a kinase that phosphorylates IRF transcription factors controlling interferon production. Mib genes selectively controlled responses to cytosolic RNA. MIB deficiency reduced antiviral activity, establishing the role of MIB proteins as positive regulators of antiviral responses. The HI5 provides a dynamic physical and regulatory network that serves as a resource for mechanistic analysis of innate immune signaling. © 2011 Elsevier Inc.

Cite

CITATION STYLE

APA

Li, S., Wang, L., Berman, M., Kong, Y. Y., & Dorf, M. E. (2011). Mapping a Dynamic Innate Immunity Protein Interaction Network Regulating Type I Interferon Production. Immunity, 35(3), 426–440. https://doi.org/10.1016/j.immuni.2011.06.014

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free