Deubiquitinase essential for the regulation of nucleolar structure and function ( ). Required for cell and organism viability ( ). Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability ( , ). Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) . Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex . In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm . Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions . Deubiquitinates SOD2, regulates SOD2 protein stability . Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins . Promotes CEP63 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability . Acts as a SUMO ligase to promote EXOSC10 sumoylation critical for the nucleolar RNA exosome function in rRNA processing . Binds to pre-rRNAs .
Subcellular locations: Nucleus, Nucleolus, Cytoplasm
Broadly expressed.