NF-kappa-B essential modulator

Definition:

Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways. Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin upon cell stimulation, with a much higher affinity for linear polyubiquitin. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.; (Microbial infection) Also considered to be a mediator for HTLV-1 Tax oncoprotein activation of NF-kappa-B.

References:

[1]. Yong-Kang Yang, et al. Molecular Determinants of Scaffold-induced Linear Ubiquitinylation of B Cell Lymphoma/Leukemia 10 (Bcl10) during T Cell Receptor and Oncogenic Caspase Recruitment Domain-containing Protein 11 (CARD11) Signaling. J Biol Chem. 2016 Dec 9;291(50):25921-25936. [Content Brief]

[2]. Yu-Chih Lo, et al. Structural basis for recognition of diubiquitins by NEMO. Mol Cell. 2009 Mar 13;33(5):602-15. [Content Brief]

[3]. Honglin Zhou, et al. Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO. Nature. 2004 Jan 8;427(6970):167-71. [Content Brief]

[4]. Sambit K Nanda, et al. Polyubiquitin binding to ABIN1 is required to prevent autoimmunity. J Exp Med. 2011 Jun 6;208(6):1215-28. [Content Brief]

[5]. Florence Cordier, et al. The zinc finger of NEMO is a functional ubiquitin-binding domain. J Biol Chem. 2009 Jan 30;284(5):2902-2907. [Content Brief]

[6]. G Xiao, et al. Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein. Oncogene. 2000 Oct 26;19(45):5198-203. [Content Brief]

[7]. Wenwen Zeng, et al. Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3. Mol Cell. 2009 Oct 23;36(2):315-25. [Content Brief]

[8]. D M Rothwarf, et al. IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature. 1998 Sep 17;395(6699):297-300. [Content Brief]

[9]. Jing Wu, et al. SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO. Cell Rep. 2021 Feb 16;34(7):108761. [Content Brief]

[10]. Chuan-Jin Wu, et al. Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]. Nat Cell Biol. 2006 Apr;8(4):398-406. [Content Brief]

[11]. Chuan-Jin Wu, et al. NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3023-8. [Content Brief]

[12]. Kei-ichiro Arimoto, et al. Polyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense. Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15856-61. [Content Brief]

[13]. D Y Jin, et al. Role of adapter function in oncoprotein-mediated activation of NF-kappaB. Human T-cell leukemia virus type I Tax interacts directly with IkappaB kinase gamma. J Biol Chem. 1999 Jun 18;274(25):17402-5. [Content Brief]

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