Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:
11923872, PubMed:
15053880, PubMed:
16964248, PubMed:
18716620, PubMed:
25283148, PubMed:
26678539, PubMed:
28655758). Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation (PubMed:
15053880, PubMed:
16845383, PubMed:
18566590, PubMed:
20153724). Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis (PubMed:
25283148). Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis (PubMed:
11923872). Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity (PubMed:
16964248). In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML (PubMed:
18716620). Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5 proteasomal-mediated degradation (PubMed:
26678539). Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV- induced degradation of ERCC6 (PubMed:
22466611, PubMed:
22466612). Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1 (PubMed:
21745816, PubMed:
22411829). Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:
25944111). Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex (PubMed:
20601937). Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo (PubMed:
20601937). Exhibits a preference towards 'Lys-48'-linked ubiquitin chains (PubMed:
22689415). Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function (PubMed:
23973222). Plays a role in the maintenance of the circadian clock periodicity via deubiquitination and stabilization of the CRY1 and CRY2 proteins (PubMed:
27123980). Deubiquitinates REST, thereby stabilizing REST and promoting the maintenance of neural progenitor cells (PubMed:
21258371). Deubiquitinates SIRT7, inhibiting SIRT7 histone deacetylase activity and regulating gluconeogenesis (PubMed:
28655758).
