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Regulation of innate immune signalling pathways by the tripartite motif (TRIM) family proteins.

Kawai T, Akira S - EMBO Mol Med (2011)

Bottom Line: These PRRs trigger distinct signal transduction pathways that culminate in induction of an array of cytokines and other mediators required for host defense.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Japan. tkawai@biken.osaka-u.ac.jp

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Related in: MedlinePlus

Recognition of retrovirus and activation of NF-κB by TRIM5TRIM5 recognizes retrovirus capsid and promotes the synthesis of unanchored ubiquitin chains linked to K63. These chains trigger a proinflammatory response by activating the TAK1 kinase complex. Binding TRIM5 to the capsid causes activation of TRIM5 E3 ubiquitin ligase activity as well as destruction of capsid to prevent infections.
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fig04: Recognition of retrovirus and activation of NF-κB by TRIM5TRIM5 recognizes retrovirus capsid and promotes the synthesis of unanchored ubiquitin chains linked to K63. These chains trigger a proinflammatory response by activating the TAK1 kinase complex. Binding TRIM5 to the capsid causes activation of TRIM5 E3 ubiquitin ligase activity as well as destruction of capsid to prevent infections.

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.


Regulation of innate immune signalling pathways by the tripartite motif (TRIM) family proteins.

Kawai T, Akira S - EMBO Mol Med (2011)

Recognition of retrovirus and activation of NF-κB by TRIM5TRIM5 recognizes retrovirus capsid and promotes the synthesis of unanchored ubiquitin chains linked to K63. These chains trigger a proinflammatory response by activating the TAK1 kinase complex. Binding TRIM5 to the capsid causes activation of TRIM5 E3 ubiquitin ligase activity as well as destruction of capsid to prevent infections.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3377094&req=5

fig04: Recognition of retrovirus and activation of NF-κB by TRIM5TRIM5 recognizes retrovirus capsid and promotes the synthesis of unanchored ubiquitin chains linked to K63. These chains trigger a proinflammatory response by activating the TAK1 kinase complex. Binding TRIM5 to the capsid causes activation of TRIM5 E3 ubiquitin ligase activity as well as destruction of capsid to prevent infections.
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.

Bottom Line: These PRRs trigger distinct signal transduction pathways that culminate in induction of an array of cytokines and other mediators required for host defense.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Japan. tkawai@biken.osaka-u.ac.jp

Show MeSH
Related in: MedlinePlus