Human Ubiquitin Carboxyl Terminal Hydrolase L5 (UCHL5) Enzyme

Background

UCHL5, also known as UCH37, is a deubiquitinating enzyme (DUB) that plays a key role in the ubiquitin-proteasome system by removing ubiquitin chains from proteasomal substrates, thereby regulating protein turnover and degradation. UCHL5 interacts with the 19S regulatory particle of the 26S proteasome, facilitating the recycling of ubiquitin to maintain cellular proteostasis. It is involved in DNA repair, cell cycle progression, and stress responses, making it crucial for cellular homeostasis. UCHL5 has also been implicated in tumorigenesis, where its overexpression promotes cell survival, proliferation, and chemoresistance by preventing the degradation of oncogenic proteins. Inhibitors of UCHL5 have shown potential as anti-cancer agents by enhancing proteasomal degradation of key regulatory proteins. Knockdown studies reveal its role in impaired cell growth, defective DNA repair, and increased apoptosis, highlighting UCHL5's importance in protein homeostasis, cellular stability, and cancer progression.