Ubiquitin specific protease 39 is a 65 kDa protein that plays an important role in pre-mRNA splicing, as well as mitotic spindle formation. It displays significant homology with ubiquitin C-terminal hydrolase proteins, containing both an N-terminal zinc finger domain as well as UCH-1 and UCH-2-like domains also observed in the UCH2 family of proteins. However, USP39 lacks a catalytic cysteine residue found in UCHs and has been shown experimentally to lack peptidase activity. USP39 associates with the U4/U6-U5 tri-small nuclear ribonucleoprotein complex and is necessary for the formation of the mature spliceosome. Silencing of USP39 has been shown to adversely affect chromosome segregation and cytokinesis in U2OS cells, likely due to improper splicing of Aurora B and other mRNAs necessary for mitotic spindle formation and checkpoint function. In addition, USP39 has been found to be overexpressed in many types of cancers, and in most cases is associated with tumor progression and poor prognosis. Overexpression has been observed in pancreatic, prostate, colorectal, lung, gastric, and triple negative breast cancers, as well as melanoma and hepatocellular carcinoma.
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