Tax1-binding protein 1

Definition:

Ubiquitin-binding adapter that participates in inflammatory, antiviral and innate immune processes as well as selective autophagy regulation. Plays a key role in the negative regulation of NF-kappa-B and IRF3 signalings by acting as an adapter for the ubiquitin-editing enzyme A20/TNFAIP3 to bind and inactivate its substrates. Disrupts the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKBKE to attenuate 'Lys63'-linked polyubiquitination of TBK1 and thereby IFN-beta production. Recruits also A20/TNFAIP3 to ubiquitinated signaling proteins TRAF6 and RIPK1, leading to their deubiquitination and disruption of IL-1 and TNF-induced NF-kappa-B signaling pathways. Inhibits virus-induced apoptosis by inducing the 'Lys-48'-linked polyubiquitination and degradation of MAVS via recruitment of the E3 ligase ITCH, thereby attenuating MAVS-mediated apoptosis signaling. As a macroautophagy/autophagy receptor, facilitates the xenophagic clearance of pathogenic bacteria such as Salmonella typhimurium and Mycobacterium tuberculosis. Upon NBR1 recruitment to the SQSTM1-ubiquitin condensates, acts as the major recruiter of RB1CC1 to these ubiquitin condensates to promote their autophagic degradation.

References:

[1]. L Ling, et al. T6BP, a TRAF6-interacting protein involved in IL-1 signaling. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9567-72. [Content Brief]

[2]. Nicolas Baillet, et al. Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses. Viruses. 2019 Mar 23;11(3):293. [Content Brief]

[3]. Amelia E Ohnstad, et al. Receptor-mediated clustering of FIP200 bypasses the role of LC3 lipidation in autophagy. EMBO J. 2020 Dec 15;39(24):e104948. [Content Brief]

[4]. Linlin Gao, et al. ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling. J Biol Chem. 2011 Oct 21;286(42):36592-602. [Content Brief]

[5]. Shichen Hu, et al. Mechanistic Insights into Recognitions of Ubiquitin and Myosin VI by Autophagy Receptor TAX1BP1. J Mol Biol. 2018 Sep 14;430(18 Pt B):3283-3296. [Content Brief]

[6]. D De Valck, et al. The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases. Oncogene. 1999 Jul 22;18(29):4182-90. [Content Brief]

[7]. Noula Shembade, et al. Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and LPS-mediated NF-kappaB and JNK signaling. EMBO J. 2007 Sep 5;26(17):3910-22. [Content Brief]

[8]. Tao Fu, et al. Mechanistic insights into the interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1. Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):E11651-E11660. [Content Brief]

[9]. Eleonora Turco, et al. Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation. Nat Commun. 2021 Sep 1;12(1):5212. [Content Brief]

[10]. Young Bong Choi, et al. TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS. Mol Cell Biol. 2016 Dec 19;37(1):e00422-16. [Content Brief]

[11]. David A Tumbarello, et al. The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy. PLoS Pathog. 2015 Oct 9;11(10):e1005174. [Content Brief]

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