Trim21 regulates Nmi-IFI35 complex-mediated inhibition of innate antiviral response.
In this study, using an immunoprecipitation coupled with mass spectrometry approach, we have identified the E3 ubiquitin ligase Trim21 as an interacting partner of IFI35 and Nmi. We found that this interaction leads to K63-linked ubiquitination on K22 residue of Nmi, but not IFI35. Using domain deletion analysis, we found that the interaction is mediated via the coiled-coil domain of Nmi and the carboxyl-terminal SPRY domain of Trim21. Furthermore, we show that depletion of Trim21 leads to significantly reduced interaction of Nmi with IFI35, which results in the abrogation of the negative regulatory function of the Nmi-IFI35 complex on innate antiviral signaling. Thus, Trim21 appears to be a critical regulator of the functions of the Nmi-IFI35 complex. Overall, the results presented here uncover a new mechanism of regulation of the Nmi-IFI35 complex by Trim21, which may have implications for various autoimmune diseases associated uncontrolled antiviral signaling.
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Nebraska, USA; Nebraska Center for Virology, University of Nebraska-Lincoln, Nebraska, USA.
Anshuman
A
Das
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Nebraska, USA; Nebraska Center for Virology, University of Nebraska-Lincoln, Nebraska, USA.
Phat X
PX
Dinh
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Nebraska, USA; Nebraska Center for Virology, University of Nebraska-Lincoln, Nebraska, USA. Electronic address: apattnaik2@unl.edu.
Asit K
AK
Pattnaik
D002352:Carrier Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012261:Ribonucleoproteins / Q000378:metabolism*; D054875:Ubiquitination; D014780:Viruses / Q000276:immunology*; D000099207:SS-A Antigen
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine; D046912:Multiprotein Complexes; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C085378:IFI35 protein, human; C099927:NMI protein, human
IFI35; ISG; Innate antiviral signaling; Nmi; Trim21; Ubiquitination