UCHL1 (Ubiquitin C-terminal Hydrolase L1) is a brain-specific deubiquitinating enzyme that plays a crucial role in various cellular processes. It is highly expressed in the brain and spinal cord neurons and is essential for maintaining proper UPS (Ubiquitin-Proteasome System) functions. It hydrolyzes free monoubiquitin from ubiquitinated proteins for recycling, ligates ubiquitin into specific proteins for proteasomal degradation, and binds to free monoubiquitin to maintain an available ubiquitin pool. UCHL1 is involved in the clearance of abnormal protein aggregates and is closely associated with several neurodegenerative diseases and CNS trauma. UCHL1 activity can protect neurons from hypoxic damage. After a stroke, reactive lipids bind to cysteine 152 (C152) of UCHL1, causing the protein to unfold and lose its function. UCHL1 is indispensable for axonal maintenance and integrity. Mutations in the UCHL1 gene in humans can lead to progressive early-onset neurodegeneration. Furthermore, UCHL1 has been implicated in various cancers, including pancreatic, colorectal, and breast cancer, where it can promote cancer invasion and metastasis
. It interacts with signaling pathways such as TGF-β and hypoxia signaling, which are important for cancer progression and metastasis.
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