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A new toolkit for monitoring endogenous ubiquitin

18 July 2012. Scientists at the Buchmann Institute for Molecular Life Sciences developed specific ubiquitin biosensors for in vivo application. This approach might mark a major technical breakthrough in detection of ubiquitin signals in living cells. It is published in today's online issue of the scientific journal Molecular Cell. Link to full article or read more.

Ubiquitin (Ub) is a small regulatory molecule which can be attached to other proteins in the cell, thereby exerting highly specific signals. Ub attachments come in many different shapes; very often chains are formed via Lysines or the first Methionine linkages between different Ub molecules involved. Due to this variability, an almost unlimited repertoire of Ub signals exists, regulating numerous processes in cells from all higher organisms.

This ubiquitous presence of Ub makes it extremely difficult to develop tools for detecting and tracing the role of the molecule in specific processes. Up to now, tools were rather rudimentary and mainly focused on the biochemical characterization of the players involved. As published in the latest online issue of Molecular Cell, a group of scientists led by Ivan Dikic managed to develop highly versatile sensors for specific Ub chains and successfully demonstrated their application in living cells.

The scientists borrowed from nature’s repertoire to design the novel biosensors. They isolated specific Ub binding domains, which proteins use to recognize Ub, and fused it to fluorescent tags. By engineering different binding domains in such a way, structurally similar Ub chains could be selectively distinguished. The scientists subsequently employed their new tools to monitor how Salmonella bacteria within the cell are tackled by the internal defense mechanisms, to monitor DNA damage responses, and to interfere with intracellular signaling pathways. The versatile applicability of this new prototypical Ub sensors, ranging from fixed to living cells, will serve as starting point to track-and-trace other types of Ub and similar signals, like SUMO or LC3. Link to full article.

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Ivan Dikic
Buchmann Institute for Molecular Life Sciences and Institute of Biochemistry II
Goethe University Frankfurt
Max von Laue Str. 15
60428 Frankfurt am Main

Tel. +49 (0)69 63015652


Full reference:
van Wijk SJL, Fiskin E, Putyrski M, Pampaloni F, Hou J, Wild P, Kensche T, Grecco HE, Bastiaens P, Dikic I (2012) Fluorescence-Based Sensors to Monitor Localization and Functions of Linear and K63-Linked Ubiquitin Chains in Cells. Molecular Cell (in press), dx.doi.org/10.1016/j.molcel.2012.06.017