Researchers discover new enzyme family
Published On Tue 14 Jun 2016 by Grant Hill
Researchers from the University of Dundee have discovered a new family of enzymes that could provide greater understanding into the development of diseases such as Alzheimer’s disease and Frontotemporal dementia.
In research published online in the journal Molecular Cell, Dr Yogesh Kulathu and colleagues from the University’s School of Life Sciences have reported the discovery of a completely new group of Deubiquitinating enzymes (DUBs). This contradicts the scientific community’s widely held belief that all families of DUBs had already been identified.
Ubiquitin signals impact on a wide range of processes in cellular biology so it is important that they are tightly regulated to prevent damage and disease. This layer of regulation is provided by DUBs, around 100 of which are encoded in the human genome and had been previously been classified into five families.
When analysing the sequence of a hitherto unstudied protein called FAM63A for another purpose, Dr Kulathu discovered deubiquitinating activity. This act of scientific serendipity may one day lead to new ways of tackling Alzheimer’s and dementia.
Dr Kulathu said, “This discovery of a new family of DUBs was totally unexpected especially since it was widely believed that all human DUBs had been found.
“With growing interest in exploring DUBs as therapeutic targets, our research expands our knowledge of the ubiquitin system and opens avenues of research into the regulation of protein degradation signals.”
The research makes FAM63A a prototype of a completely new family of DUBs that the team named MINDY. MINDY DUBs are highly selective at cleaving the signal that targets proteins for proteasomal degradation. When proteins aren’t degraded properly, misfolded and aggregated proteins can accumulate. This is a common contributing factor to Alzheimer’s, dementia and other age-related diseases.
Professor Dario Alessi, Director of the University’s Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU), said, “I congratulate Yogesh and his team for this stunning piece of research.
“This work was surprising as I thought that all the DUBs had been identified and catalogued a long time ago. It emphasises that we don’t know everything and there is still lots of important biology out there just waiting to be uncovered.
“Above all, this work illustrates the importance of curiosity driven research that one is able to undertake in the core-funded environment of an MRC Unit. It is going to be exciting to see what roles the MINDY DUBs play in regulating biology in future research.”
This work, carried out by Dr Kulathu and Dr Syed Arif Abdul Rehman, Dr Soo-Youn Choi and Yosua Kristariyanto, with help from Professor Kay Hofmann at the University of Cologne, was funded by the Medical Research Council.
The Kulathu lab has recently obtained additional funding from Tenovus Scotland to hire a postdoctoral researcher to unravel roles for this new family of enzymes in maintaining protein homeostasis.
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