Ubiquitin thioesterase OTUB1 (OTUB1) (OTUB1)

Ubiquitin thioesterase OTUB1, also known as Otubain-1, is a highly specific deubiquitinating enzyme (DUB) belonging to the ovarian tumor (OTU) family (UniProt Q96FW1). It primarily cleaves Lys-48-linked polyubiquitin chains, thereby preventing the proteasomal degradation of its target proteins (PubMed: 12913066). Uniquely, OTUB1 also exerts a non-catalytic inhibitory effect on the ubiquitination machinery by binding to and sequestering E2 ubiquitin-conjugating enzymes, such as UBE2N and the UBE2D family (PubMed: 21107328). This dual mechanism allows OTUB1 to regulate critical cellular processes including DNA damage repair, TGF-beta signaling, and protein homeostasis. In clinical contexts, OTUB1 is frequently overexpressed in various malignancies, where it stabilizes oncogenic drivers like FOXM1 and p53, promoting tumor progression and drug resistance (PubMed: 25201290). Consequently, it has emerged as a promising therapeutic target, with research focusing on small molecule inhibitors like OTUB1-IN-1 designed to block its activity (PubMed: 32810024).

Other names

Otubain-1OTU domain-containing ubiquitin aldehyde-binding protein 1HSPC263OTB1

Inhibition of deubiquitinase catalytic activity and disruption of non-catalytic E2 enzyme sequestration