ZUP1 and cancer: UCHL1 is one such DUB that has recently been shown to promote HIF1α deubiquitination in a variety of cancer cell types [9,25], although it is not clear if UCHL1 can deubiquitinate HIF1a directly due to restricted access of the active site resulting from the narrow channel formed by surrounding residues, this limiting substrate entry and influencing enzymatic activity [34].