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Ubiquitin carboxyl-terminal hydrolase 10

Definition:

Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling. Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage. Deubiquitinates TBX21 leading to its stabilization.

References:

[1]. Jian Yuan, et al. USP10 regulates p53 localization and stability by deubiquitinating p53. Cell. 2010 Feb 5;140(3):384-96. [Content Brief]

[2]. Lina Pan, et al. Deubiquitination and stabilization of T-bet by USP10. Biochem Biophys Res Commun. 2014 Jul 4;449(3):289-94. [Content Brief]

[3]. Junli Liu, et al. Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell. 2011 Sep 30;147(1):223-34. [Content Brief]

[4]. C Soncini, et al. Ras-GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel human ubiquitin specific protease. Oncogene. 2001 Jun 28;20(29):3869-79. [Content Brief]

[5]. Jennifer M Bomberger, et al. The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of cystic fibrosis transmembrane conductance regulator in airway epithelial cells. J Biol Chem. 2009 Jul 10;284(28):18778-89. [Content Brief]

[6]. Sheerazed Boulkroun, et al. Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface expression by deubiquitylating and stabilizing sorting nexin 3. Am J Physiol Renal Physiol. 2008 Oct;295(4):F889-900. [Content Brief]

[7]. Wei Wang, et al. TRAF Family Member-associated NF-κB Activator (TANK) Inhibits Genotoxic Nuclear Factor κB Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase. J Biol Chem. 2015 May 22;290(21):13372-85. [Content Brief]

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