SCILLS - The Scottish Institute for Cell Signalling

SCILLS is dedicated to the study of how biological processes are controlled and how they become deregulated in disease. The Protein Ubiquitination Unit is the Institute's first research Division. Its major aims are to advance understanding of the role of protein ubiquitination and related modifications in cell regulation and human disease, to facilitate the development of drugs to treat diseases caused by abnormalities in this process, to generate reagents and improve technologies on which more rapid progress in this area depends, and to train the next generation of scientists who will advance the subject.

An article published by SCILLS researchers in the Biochemical Journal reports the finding that the cancer drug Bortezomib may elicit some of its anti-cancer effects by a process called “atypical neddylation” (Hjerpe R. et al. Biochem J. 2011 Oct 17). The work, performed by postdoctoral fellow Roland Hjerpe in the research group of Thimo Kurz, reports that the ubiquitin-like molecule NEDD8 can be conjugated to proteins through enzymes of the related ubiquitin pathway. Under conditions where the ratio of NEDD8 to ubiquitin is increased in cells, robust activation of NEDD8 by the ubiquitin-activating enzyme occurs. This activation leads to atypical neddylation of substrate proteins through the E2 and E3 enzymes of the ubiquitin pathway.		Roland Hjerpe
Circumstances inducing atypical neddylation include treatment with the anti-cancer drug Bortezomib and other proteasome inhibitors. Atypical neddylationattenuates ubiquitin dependent proteasomal degradation, which may in part be how Bortezomib mediates prolonged inhibition of protein degradation and cytotoxicity. This report is the first paper to be published from a SCILLS junior PI. Click here