OTUB2 is a member of the OTU (ovarian tumor) deubiquitinase family, encoded by the OTUB2 gene (HGNC: 20351, UniProt: Q96DC9). It hydrolyzes ubiquitin-protein conjugates, preferentially cleaving Lys63-linked polyubiquitin chains, and stabilizes substrates like PD-L1 in cancer cells . OTUB2 is implicated in:
Immune evasion: Stabilizing PD-L1 to suppress CD8+ T-cell cytotoxicity .
Cancer progression: Promoting tumor growth via Hippo, AKT/mTOR, and NF-κB signaling pathways .
Ribosome recycling: Assisting in 40S ribosomal subunit maturation and translation reset .
PD-L1 Regulation: OTUB2 antibodies validated OTUB2’s role in stabilizing PD-L1 by blocking its ubiquitination in the endoplasmic reticulum. Knockdown of OTUB2 reduced PD-L1 surface expression, enhancing CD8+ T-cell-mediated tumor killing .
Clinical Correlation: In non-small cell lung cancer (NSCLC), OTUB2 expression inversely correlates with CD8+ T-cell infiltration and patient survival .
OTUB2 Inhibitors: Antibodies aided in characterizing OTUB2-IN-1, a small-molecule inhibitor that reduces PD-L1 levels and suppresses tumor growth in preclinical models .
Proteintech (12066-1-AP): Detects OTUB2 at ~27 kDa in mouse and rat testis lysates .
Sigma-Aldrich (SAB1407928): Validated for human samples with a working concentration of 1 µg/mL .
Mechanistic Role: OTUB2 stabilizes PD-L1 by counteracting endoplasmic reticulum-associated degradation (ERAD), making it a therapeutic target for immune checkpoint blockade .
Disease Linkage: High OTUB2 expression correlates with poor prognosis in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) .
KEGG: spo:SPAC1952.03
STRING: 4896.SPAC1952.03.1