Ubiquitin carboxyl-terminal hydrolase 16 (USP16) (USP16)

Ubiquitin carboxyl-terminal hydrolase 16 (USP16) is a deubiquitinating enzyme that plays a critical role in regulating the cell cycle and chromatin structure by specifically removing ubiquitin from histone H2A at Lys-119 (UniProt Q9Y5T5). This enzymatic activity is essential for proper chromosome alignment and segregation during mitosis, as well as for the maintenance of gene expression patterns in various stem cell populations (Joo et al., Nature 2007). USP16 is encoded on chromosome 21, and its overexpression is a significant factor in the pathophysiology of Down syndrome, where it contributes to the premature exhaustion of hematopoietic and neural stem cells (Adorno et al., Nature 2013). In oncology, USP16 has been implicated in the progression of several malignancies, including breast and colon cancer, by modulating signaling pathways such as Wnt/beta-catenin (Xu et al., Nature Communications 2021). While there are currently no FDA-approved drugs targeting USP16, it is an active area of research for developing small-molecule inhibitors aimed at treating Down syndrome-related phenotypes and certain cancers. Therapeutic targeting of USP16 seeks to restore the homeostatic balance of histone ubiquitination to normalize cellular proliferation and differentiation.

Other names

Deubiquitinating enzyme 16Ubiquitin-specific-processing protease 16UBP-MUbiquitin-specific protease 16

Inhibition of the deubiquitinating activity of USP16 to restore histone H2A ubiquitination levels or modulate cell cycle progression and stem cell self-renewal.