Tripartite Motif (TRIM) 12c, a Mouse Homolog of TRIM5, Is a Ubiquitin Ligase That Stimulates Type I IFN and NF-κB Pathways along with TNFR-Associated Factor 6.
Tripartite motif (TRIM) protein TRIM5 of the primate species restricts replication of HIV and other retroviruses. Whereas primates have a single TRIM5 gene, the corresponding locus in the mouse has expanded during evolution, now containing more than eight related genes. Owing to the complexity of the genomic organization, a mouse homolog of TRIM5 has not been fully studied thus far. In the present study, we report that Trim12c (formerly Trim12-2) encodes a TRIM5-like protein with a ubiquitin ligase activity. Similar to the primate TRIM5, TRIM12c is expressed in the cytoplasm as a punctate structure and induced upon IFN and pathogen stimulation in macrophages and dendritic cells. We show that TRIM12c interacts with TRAF6, a key protein in the pathogen recognition receptor signaling, and reciprocally enhances their ubiquitination, leading to cooperative activation of IFN and NF-κB pathways. This study identifies TRIM12c as a mouse TRIM5 equivalent, critical for host innate immunity.
Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD, 20892; and Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 81362.
Tsung-Hsien
http://orcid.org/0000-0003-4806-7864
TH
Chang
Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD, 20892; and.
Ryusuke
http://orcid.org/0000-0002-3945-307X
R
Yoshimi
Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD, 20892; and ozatok@nih.gov.
Keiko
K
Ozato
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D002352:Carrier Proteins; D007370:Interferon Type I; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; D000070584:Tripartite Motif Proteins; C541472:TRIM5 protein, mouse; D044767:Ubiquitin-Protein Ligases; C000605779:TRIM12c protein, mouse