Human cells have a sophisticated regulatory system that consists of labeling proteins with the 

small molecule ubiquitin. In a first, a team from the Technical University of Munich (TUM) has 

succeeded in marking proteins with ubiquitin in a targeted manner in test tubes as well as in 

living  cells.  The  procedure  opens  the  door  to  exploring the inner workings of this vital 

regulatory system.

Plants, fungi, animals and humans express the protein ubiquitin. It comprises a sequence of 

76 amino acids, making it a relatively small biomolecule. But its influence is far-reaching: the 

type, position and number of ubiquitin molecules bound to proteins determine their stability, 

function, and location within the cell.

"Virtually every process in the cell is directly or indirectly affected by ubiquitin. That is why 

malfunctions of this labeling mechanism are associated with the development and progress

ion of cancer and many other severe diseases," explains Kathrin Lang, Professor of Synthetic 

Biochemistry at the Technical University of Munich.

The discovery of the important role this cellular regulatory system plays in the controlled 

degradation of proteins was acknowledged with the 2004 Nobel Prize in Chemistry. But, in 

many cases the details of how ubiquitin modifications affect the function of cells remains 

unclear. Kathrin Lang's team has now developed a method for attaching ubiquitin labels to 

targeted proteins—a key to exploring the system.

A bacterial enzyme creates new compounds

Lang's team uses two tricks to circumvent the complicated natural system: They incorporate a 

novel modified amino acid, at which the bacteria-derived enzyme sortase can attach ubiquitin 

or a ubiquitin-similar molecule.