E3 ubiquitin-protein ligase TRIM8

Definition:

E3 ubiquitin-protein ligase that participates in multiple biological processes including cell survival, differentiation, apoptosis, and in particular, the innate immune response. Participates in the activation of interferon-gamma signaling by promoting proteasomal degradation of the repressor SOCS1. Plays a positive role in the TNFalpha and IL-1beta signaling pathways. Mechanistically, induces the 'Lys-63'-linked polyubiquitination of MAP3K7/TAK1 component leading to the activation of NF-kappa-B. Modulates also STAT3 activity through negative regulation of PIAS3, either by degradation of PIAS3 through the ubiquitin-proteasome pathway or exclusion of PIAS3 from the nucleus. Negatively regulates TLR3/4-mediated innate immune response by catalyzing 'Lys-6'- and 'Lys-33'-linked polyubiquitination of TICAM1 and thereby disrupting the TICAM1-TBK1 interaction.

References:

[1]. Elena Toniato, et al. TRIM8/GERP RING finger protein interacts with SOCS-1. J Biol Chem. 2002 Oct 4;277(40):37315-22. [Content Brief]

[2]. Fumihiko Okumura, et al. TRIM8 modulates STAT3 activity through negative regulation of PIAS3. J Cell Sci. 2010 Jul 1;123(Pt 13):2238-45. [Content Brief]

[3]. Wen Ye, et al. TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction. J Immunol. 2017 Sep 1;199(5):1856-1864. [Content Brief]

[4]. Feng-Juan Yan, et al. The E3 ligase tripartite motif 8 targets TAK1 to promote insulin resistance and steatohepatitis. Hepatology. 2017 May;65(5):1492-1511. [Content Brief]

[5]. Dhanendra Tomar, et al. Nucleo-cytoplasmic trafficking of TRIM8, a novel oncogene, is involved in positive regulation of TNF induced NF-κB pathway. PLoS One. 2012;7(11):e48662. [Content Brief]

[6]. Qi Li, et al. Tripartite motif 8 (TRIM8) modulates TNFα- and IL-1β-triggered NF-κB activation by targeting TAK1 for K63-linked polyubiquitination. Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19341-6. [Content Brief]

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