DUB1 Activators

USP36, a member of the ubiquitin-specific protease family, functions as a cysteine protease involved in deubiquitinating polyubiquitinated proteins. Its known role includes the deubiquitination and stabilization of the transcription factor c-Myc, a crucial oncoprotein upregulated in various human cancers. Additionally, USP36 is implicated in the regulation of autophagy, adding another layer of complexity to its cellular functions. Elevated expression of USP36 is observed in certain breast and lung cancers, emphasizing its potential significance in tumorigenesis.

Activation of USP36 involves a dynamic interplay with various chemical modulators targeting specific cellular pathways. Direct activators like Nutlin-3 and MLN4924 impact c-Myc stabilization by disrupting its ubiquitin-proteasome pathway and neddylation, respectively. Indirect activators, such as Rapamycin and Chloroquine, influence autophagy, indirectly up-regulating USP36 by modulating cellular processes. Compounds like JQ1 and C646 indirectly affect USP36 by interfering with bromodomain or histone acetylation, influencing c-Myc expression and stability. The activation of USP36 is intricately linked to the regulation of c-Myc and autophagy, highlighting its role in maintaining protein homeostasis and cellular processes crucial for cancer development. Understanding the diverse mechanisms of USP36 activation provides insights into its potential as a target and the intricate network of pathways it modulates in cancer biology.