OTU domain-containing protein 7B

Definition:

Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses. In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B. Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR. Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains. Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure. Hydrolyzes both linear and branched forms of polyubiquitin.

References:

[1]. Paul C Evans, et al. A novel type of deubiquitinating enzyme. J Biol Chem. 2003 Jun 20;278(25):23180-6. [Content Brief]

[2]. P C Evans, et al. Isolation and characterization of two novel A20-like proteins. Biochem J. 2001 Aug 1;357(Pt 3):617-23. [Content Brief]

[3]. F Pareja, et al. Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression. Oncogene. 2012 Oct 25;31(43):4599-608. [Content Brief]

[4]. Tycho E T Mevissen, et al. Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne. Nature. 2016 Oct 20;538(7625):402-405. [Content Brief]

[5]. Hongbo Hu, et al. Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination. J Exp Med. 2016 Mar 7;213(3):399-414. [Content Brief]

[6]. Tycho E T Mevissen, et al. OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis. Cell. 2013 Jul 3;154(1):169-84. [Content Brief]

[7]. Anja Bremm, et al. Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne. Nat Struct Mol Biol. 2010 Aug;17(8):939-47. [Content Brief]

[8]. Karine Enesa, et al. NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling. J Biol Chem. 2008 Mar 14;283(11):7036-45. [Content Brief]

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