title: Mapping a dynamic innate immunity protein interaction network regulating type I interferon production.
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.
authors: Division of Immunology, Department of Microbiology & Immunobiology, Harvard Medical School, Boston, MA 02115, USA. lishitao@hotmail.com
authors: Shitao
authors: S
authors: Li
authors: Lingyan
authors: L
authors: Wang
authors: Michael
authors: M
authors: Berman
authors: Young-Yun
authors: YY
authors: Kong
authors: Martin E
authors: ME
authors: Dorf
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D051379:Mice; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D040901:Proteomics; D054875:Ubiquitination; D014777:Virus Diseases / Q000276:immunology; D014780:Viruses / Q000276:immunology
chemical_list: D007370:Interferon Type I; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human