BRISC complex subunit Abraxas 2

Definition:

Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates. May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm. Plays a role in regulating the onset of apoptosis via its role in modulating 'Lys-63'-linked ubiquitination of target proteins (By similarity). Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activities by enhancing its stability and cell surface expression. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination. Required for normal induction of p53/TP53 in response to DNA damage. Independent of the BRISC complex, promotes interaction between USP7 and p53/TP53, and thereby promotes deubiquitination of p53/TP53, preventing its degradation and resulting in increased p53/TP53-mediated transcription regulation and p53/TP53-dependent apoptosis in response to DNA damage.

References:

[1]. Hui Zheng, et al. A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses. Cell Rep. 2013 Oct 17;5(1):180-93. [Content Brief]

[2]. Jianhong Zhang, et al. ABRO1 suppresses tumourigenesis and regulates the DNA damage response by stabilizing p53. Nat Commun. 2014 Oct 6;5:5059. [Content Brief]

[3]. Elton Zeqiraj, et al. Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function. Mol Cell. 2015 Sep 17;59(6):970-83. [Content Brief]

[4]. Eric M Cooper, et al. K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1. EMBO J. 2009 Mar 18;28(6):621-31. [Content Brief]

[5]. Kaowen Yan, et al. The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells. J Cell Biol. 2015 Jul 20;210(2):209-24. [Content Brief]

[6]. Eric M Cooper, et al. Specificity of the BRISC deubiquitinating enzyme is not due to selective binding to Lys63-linked polyubiquitin. J Biol Chem. 2010 Apr 2;285(14):10344-52. [Content Brief]

[7]. Lin Feng, et al. The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments. J Biol Chem. 2010 Oct 1;285(40):30982-8. [Content Brief]

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