Together with the group of Yogesh Kulathu, based at the MRC PPU, University of Dundee, we’ve contributed to the discovery of a new K63-specific deubiquitinating enzyme (DUB) family, which consists solely of a protein called ZUFSP/ZUP1 in humans. The findings are published as open-access here:
The wonderful biochemical and structural findings are supported with an initial investigation of ZUP1 function in cells, which points towards this novel DUB family as having a role in genome stability pathways.
Three other groups (Niels Mailand, Kay Hofmann and Ingrid Wertz) also independently discovered that ZUP1 is capable of cleaving K63 chains, corroborating our findings. There are unique elements of each paper, so it's useful to read them all.
Despite these efforts there is clearly still a long way to go to understanding the detailed mechanism and function of ZUP1. Given that ZUP1 is a novel DUB family, will it be amenable to drug inhibition? Recent work by several groups on USP7 inhibitors certainly provides hope. Therefore, a deeper understanding of the role of ZUP1 in normal and cancer cells will be essential in the future if we are to exploit these findings for therapeutic purposes.
For more information on Yogesh Kulathu’s research, please see his group website:
After receiving a CRUK Career Development Fellowship, I will be joining the Department of Biochemistry, University of Oxford, as a Principal Investigator, with the lab open May 2018.
DPhil (PhD) students wishing to join the lab should apply through the Department of Biochemistry (January 8th 2018 deadline):
Postdoctoral opportunities will be advertised in the near future. Please get in touch to discuss possibilities to join the lab.