Ubiquitin thioesterase ZRANB1 (ZRANB1)

Ubiquitin thioesterase ZRANB1 (ZRANB1, also known as TRABID) is a multi-domain cysteine protease of the ovarian tumor (OTU) deubiquitinase family that hydrolyzes K29-, K33-, and to a lesser extent K63-linked polyubiquitin chains from substrate proteins. It contains three N-terminal NZF domains, a central ankyrin repeat domain, and a C-terminal OTU catalytic domain. ZRANB1 regulates the stability and activity of critical cellular proteins such as EZH2 (the catalytic subunit of PRC2), supports cell proliferation and migration (notably in triple-negative breast cancer), and is implicated in Wnt signaling and autophagic processes. It is abundantly expressed in various cancer cell lines but is low or undetectable in most normal tissues. Pharmacological and genetic inhibition of ZRANB1 leads to anti-cancer effects through destabilization of EZH2 and disruption of oncogenic pathways, nominating it as a potential therapeutic target, mainly in oncology.

Other names

Zinc finger RANBP2-type containing 1TRABIDhTrabidTRAF-binding domain-containing proteinZinc finger Ran-binding domain-containing protein 1Zinc finger, RAN-binding domain containing 1

Inhibition of deubiquitinase activity: Small molecules such as NSC112200 block the catalytic activity of ZRANB1, preventing it from deubiquitinating targets like EZH2.