Overview:

USP28 (ubiquitin carboxyl-terminal hydrolase 28) is a deubiquitinase belonging to the family of deubiquitinating enzymes (DUBs) and plays a role in the DNA damage pathway by specifically deubiquitinating proteins of the pathway such as CLSPN. USP2 deubiquitinates ZNF304, inhibiting its degradation and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in various colorectal cancers (CRC) cells (1). USP28 counteracts the activity of E3 ligases, antagonizes FBW7 and a component of the SCF-type E3 ubiquitin ligase that targets key transcriptional factors to ubiquitin-directed proteasome degradation, thus stabilizing substrates such as oncogenic c-MYC (2). This may lead to enhanced proliferation, carcinogenesis, and metastasis.

Gene Aliases:

KIAA1515

Genbank Number:

NM_020886

References:

1. Serra, Ryan W et al: A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. eLife 3: e02313, 2014.

2. Wang, X. et al: Targeting deubiquitinase USP28 for cancer therapy. Cell Death & Disease 9: 186, 2018.