CPR researchers quantify thousands of endogenous ubiquitylation sites

CPR researchers quantify thousands of endogenous ubiquitylation sites
Modification of proteins by ubiquitin can serve as a ‘kiss of death' to target proteins for degradation via the proteasome. However, it is clearly emerging that ubiquitin also plays many other important functions in cells. Thus precise mapping of modification sites and their quantification has remained a major challenge.

The Department of Proteomics (Sebastian A. Wagner, Petra Beli, Brian T. Weinert, Michael L. Nielsen, Matthias Mann and Chunaram Choudhary) has in collaboration with the Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany recently published the largest ubiquitylation dataset in human cells to date. In this paper, for the first time, researchers were able to quantify changes in thousands of endogenous ubiquitylation sites in cells treated with a drug that inhibits ubiquitin-mediated protein degradation via the proteasome.

Wagner et al. precisely map more than 11.000 endogenous putative ubiquitylation sites, of which over 90% represent novel previously non-reported sites. The study significantly expands the number of currently known human ubiquitylation sites and will serve as a valuable resource for future functional characterization of many proteins. They show that ubiquitylation targets proteins involved in all major cellular functions and report that nearly half of all sites were shown to have nonproteasomal functions. They conclude that the regulatory scope of ubiquitylation is comparable to other post translational modifications such as phosphorylation and acetylation. The novel approach described in this paper is generic, and opens new avenues for global quantification of ubiquitylation changes in cells and tissues.

Citation: Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. MCP Papers in Press. Published on September 1, 2011 as Manuscript M111.013284.
Email: chuna.choudhary@cpr.ku.dk