Ubiquitin-specific protease 36 (USP36)

Ubiquitin-specific protease 36 (USP36) is a nucleolar deubiquitinating enzyme (DUB) and cysteine protease that belongs to the ubiquitin-specific protease family. USP36 removes ubiquitin moieties from various protein substrates, thereby regulating their stability, localization, and function. It is essential for nucleolar structure and ribosomal biogenesis by stabilizing proteins such as c-Myc, NPM1 (nucleophosmin), fibrillarin, and DHX33[1][2][3][5]. USP36 also regulates gene expression by deubiquitinating histone H2B and repressing transcription at certain promoters. It controls the degradation of c-Myc in the nucleolus and functions in ribosome biogenesis, autophagy regulation, and the cellular response to oxidative stress. USP36 has been implicated in several disease processes, especially cancer, where it is frequently overexpressed and linked to tumor proliferation and survival. Its pivotal cellular functions underline its potential as a therapeutic target, though full inhibition carries significant safety concerns due to its role in cell and organism viability[1][2][3][5].

Other names

Ubiquitin carboxyl-terminal hydrolase 36KIAA1453FLJ12851Deubiquitinating enzyme 36Ubiquitin thioesterase 36Ubiquitin-specific-processing protease 36DUB1

Inhibition or modulation of USP36 could stabilize or destabilize its substrates, affecting protein degradation pathways in the nucleolus, and could impair cell proliferation or ribosomal biogenesis, notably in cancer. No direct small-molecule inhibitors or clinically used drugs are currently well established or cited in recent literature or major databases.