USP35 Inhibitors

USP35 inhibitors belong to a class of chemical compounds that target the activity of the ubiquitin-specific protease 35 (USP35), a member of the deubiquitinating enzyme (DUB) family. USP35 is responsible for regulating the ubiquitin-proteasome system (UPS), which plays a crucial role in maintaining cellular protein homeostasis. This enzyme catalyzes the removal of ubiquitin from substrates, preventing their degradation by the proteasome. Inhibiting USP35 disrupts the normal function of the UPS by stabilizing ubiquitinated proteins, leading to alterations in various cellular processes, such as signal transduction, DNA repair, and protein turnover. The ability of USP35 inhibitors to modulate these pathways makes them particularly relevant for studies involving protein dynamics and cellular stress responses, as well as in research focused on understanding how cells maintain homeostasis in response to protein misfolding and aggregation.

Chemically, USP35 inhibitors are often designed to interact with the catalytic domain of the enzyme, typically the cysteine protease domain, where they interfere with the cleavage of ubiquitin from substrate proteins. These inhibitors can vary widely in structure, ranging from small molecules to larger, more complex compounds that mimic the enzyme's natural substrates or bind to allosteric sites. The specificity of USP35 inhibitors is an area of interest, as their structural characteristics can significantly influence their ability to selectively inhibit USP35 over other DUB family members. This specificity is often achieved by exploiting unique residues or conformational features in the USP35 catalytic site, allowing researchers to dissect the enzyme's role in various cellular pathways. As research continues, these inhibitors provide valuable insights into the regulatory mechanisms of protein ubiquitination and the broader implications of proteostasis in cellular biology.