Ubiquitin specific peptidase 26 (USP26)

Ubiquitin specific peptidase 26 (USP26) is an X-linked, testis-expressed deubiquitinating enzyme that belongs to the ubiquitin-specific protease (USP) family[3][5]. It catalyzes the removal of ubiquitin from specific substrate proteins, thereby regulating their degradation and turnover through the ubiquitin–proteasome system[5]. USP26 is critical for normal spermatogenesis and male fertility, acting in spermatogonia to prevent premature protein degradation required for sperm maturation[5]. It is also implicated in modulating key signaling pathways, including the regulation of androgen receptor activity (thus influencing male reproductive development and prostate cancer biology)[2], antagonizing TGF-β signaling via stabilization of SMAD7 (affecting cancer cell signaling and survival)[4], and stabilizing the Hippo pathway effector TAZ, promoting cancer cell proliferation and migration in anaplastic thyroid cancer[1]. Defects or loss of function in USP26 are associated with male infertility syndromes such as Sertoli cell-only syndrome and azoospermia[3][5]. Its varied roles in signaling, cell cycle regulation, and tissue specificity make it a candidate therapeutic target in oncology and male health[1][2][4][5].

Other names

Ubiquitin carboxyl-terminal hydrolase 26Deubiquitinating enzyme 26Ubiquitin thioesterase 26Ubiquitin-specific-processing protease 26SPGFX6Ubiquitin-specific protease 26Ubiquitin thiolesterase 26

Deubiquitination of substrate proteins such as TAZ and SMAD7, stabilization of androgen receptor, regulation of TGF-β signaling via SMAD7 stabilization