What does YUH mean in UNCLASSIFIED

YUH is a cysteine protease that specifically cleaves ubiquitin (Ub) from its targets. Unlike other deubiquitinases (DUBs), YUH does not contain a catalytic triad of cysteine, histidine, and asparagine residues. Instead, it employs a unique catalytic dyad of cysteine and histidine residues for its activity. YUH plays a crucial role in regulating various cellular processes, including protein degradation, signal transduction, and DNA repair.

YUH hydrolyzes the isopeptide bond between ubiquitin and its target protein, thereby releasing ubiquitin from the conjugate. It employs a unique catalytic dyad of cysteine and histidine residues for its activity. The cysteine residue acts as the nucleophile, attacking the carbonyl carbon of the isopeptide bond, while the histidine residue acts as the general base, abstracting a proton from the cysteine thiol group. This results in the formation of a tetrahedral intermediate, which subsequently collapses to release ubiquitin and the target protein.

YUH plays a crucial role in regulating various cellular processes, including:

• Protein degradation: YUH is involved in the ubiquitin-proteasome pathway, which is responsible for degrading damaged or misfolded proteins. It cleaves ubiquitin from polyubiquitinated proteins, targeting them for degradation by the proteasome.

• Signal transduction: YUH regulates signal transduction pathways by deubiquitinating signaling proteins. This can either activate or inhibit signaling cascades, depending on the specific target protein.

• DNA repair: YUH is involved in DNA repair processes, such as nucleotide excision repair (NER). It deubiquitinates proteins involved in NER, facilitating the repair of damaged DNA.

Targeting YUH has potential therapeutic applications in various diseases, including:

• Cancer: YUH is overexpressed in many types of cancer, where it contributes to tumor growth and progression. Inhibiting YUH activity could be a potential strategy for treating cancer.

• Neurodegenerative diseases: YUH dysfunction has been implicated in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Modulating YUH activity could be a potential therapeutic approach for these diseases.

• Immune disorders: YUH plays a role in regulating immune responses. Targeting YUH could be beneficial for treating immune disorders, such as autoimmune diseases and allergies.