Regulation of innate immune signalling pathways by the tripartite motif (TRIM) family proteins.
Bottom Line: The innate immune system recognizes microbial components through pattern-recognition receptors (PRRs), including membrane-bound Toll-like receptors and cytosolic receptors such as RIG-I-like receptors and deoxyribonucleic acid (DNA) sensors.The tripartite motif (TRIM) family is a diverse family of RING finger domain-containing proteins, which are involved in a variety of cellular functions.Importantly, recent studies have shown that they are also involved in the regulation of innate immune responses through the modulation of PRR signalling pathways.
Affiliation: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Japan. email@example.comShow MeSH
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Mentions: TRIM5 is known to restrict infection of retroviruses such as HIV-1 by binding to the viral capsid and inducing premature uncoating. Petrel et al recently showed that TRIM5 has a role in eliciting inflammatory responses to retroviral capsids (Fig 4). Overexpression of human TRIM5 activates signalling pathways that lead to the activation of both NF-κB and AP-1, and conversely, TRIM5 knockdown decreases the expression of NF-κB- and AP1-dependent genes involved in inflammatory responses (Pertel et al, 2011). TRIM5 was found to bind to the TAK1 complex (TAK1, TAB2 and TAB3) and E2 ubiquitin conjugation enzymes UBC13 and UEV1A, which promote the synthesis of unattached ubiquitin chains linked to K63. This results in the activation of TAK1 and subsequent induction of the expression of NF-κB- and AP1-dependent genes. Interestingly, TRIM5 binding to the HIV-1 capsid lattice enhances TRIM5 E3 ubiquitin ligase activity. Thus, TRIM5 acts as a PRR that recognizes the retrovirus capsid and activates the TAK-1-dependent inflammatory signalling pathways.
Affiliation: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Japan. firstname.lastname@example.org