Usp36-KO Mouse

Usp36, a member of the USP family of deubiquitinating enzymes, plays a crucial role in the balance between ubiquitination and deubiquitination, hydrolyzing and removing ubiquitin chains from target proteins. It is involved in various cellular events such as gene transcription regulation, cell cycle regulation, and immune responses, which are essential for maintaining cellular homeostasis [8].

In cancer, Usp36 has been implicated in promoting tumorigenesis and drug resistance. In breast cancer, it deubiquitinates and stabilizes ERα, promoting tumorigenesis and tamoxifen resistance [2]. In colorectal cancer, Usp36 inhibits apoptosis by deubiquitinating cIAP1 and survivin, and promotes cancer progression by inhibiting the p53 signaling pathway via stabilizing RBM28 [3,4]. In glioblastoma, it deubiquitinates and stabilizes ALKBH5, promoting tumorigenesis and affecting drug sensitivity [5]. In esophageal squamous carcinoma, USP36 stabilizes YAP to facilitate cancer progression [6]. Also, in non-small cell lung cancer, a germline USP36 mutation confers resistance to EGFR-TKIs by upregulating MLLT3 expression [10]. Additionally, in doxorubicin-induced cardiomyopathy, Dox promotes disease progression by activating USP36-mediated PARP1 deubiquitination [7]. In ribosome biogenesis, USP36 acts as a SUMO ligase to promote EXOSC10 SUMOylation, which is critical for the RNA exosome function in rRNA processing [9]. In solid tumors, ribotoxic stress activates the JNK-USP36 signaling to stabilize Snail1 in the nucleolus, facilitating ribosome biogenesis and tumor cell survival, and contributing to resistance to the ribosome inhibitor homoharringtonine (HHT) [1].

In conclusion, Usp36 is a multifunctional deubiquitinating enzyme with significant implications in cancer and other diseases. Studies using in vivo models such as xenograft models in breast cancer [2] and intracranial tumor growth assays in glioblastoma [5] have helped reveal its role in promoting tumorigenesis and drug resistance. These findings suggest that targeting Usp36 could be a potential therapeutic strategy for treating related diseases.