Ubiquitin carboxyl-terminal hydrolase 12 (USP12)

Ubiquitin carboxyl-terminal hydrolase 12 (USP12) is a member of the ubiquitin-specific protease family of deubiquitinating enzymes. It functions as a cysteine protease that removes ubiquitin moieties from specific protein substrates, thereby regulating protein stability and function. USP12 requires cofactors UAF1 (WD repeat-containing protein 48) and WDR20 for optimal enzymatic activity[4]. USP12 has been shown to stabilize the androgen receptor and enhance its transcriptional activity, playing a role in prostate cancer cell proliferation[4]. It also regulates pro-apoptotic proteins such as Bax through specific removal of K63-linked ubiquitin chains[2], and has additional reported roles in regulating protein phosphatases like PHLPP and PHLPPL as well as protecting neurons from huntingtin-induced toxicity[5][6]. USP12 is implicated in diseases such as cancer and neurodegeneration, but there are currently no approved drugs targeting this enzyme. Its functional importance in ubiquitin-mediated signaling makes it a potentially valuable therapeutic target under investigation.

Other names

Ubiquitin specific peptidase 12UBH1USP12L1Deubiquitinating enzyme 12Ubiquitin thioesterase 12Ubiquitin-hydrolyzing enzyme 1Ubiquitin-specific-processing protease 12

Inhibition or activation of deubiquitinating activity, leading to altered stability of specific substrates (e.g., androgen receptor, Bax, PHLPP) - Modulation of proteostasis and cell signaling by regulation of ubiquitin chain removal