No 21/October 19, 2005

MDC Researchers Identify Crucial Helper in Cellular Trash Disposal

Researchers at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have identified a crucial helper in cellular trash disposal. It delivers defective proteins, which have been tagged for disposal, to the transporter that will bring them to the cell’s shredder, the proteasomes. When this helper, called Ubx2 for short, is missing, the cellular disposal system is dysfunctional and many defective proteins will not be destroyed. As a consequence, diseases like Alzheimer’s, Parkinson’s, or mucoviscidosis can develop. The paper of Oliver Neuber and Dr. Thomas Sommer has now appeared in Nature Cell Biology (October 2005, Vol. 7, Nr. 10, pp. 993-998)*

A cell contains tens of thousands of proteins, the building materials, and the machinery of life. What happens to the proteins that are no longer needed or to the ones that are defectively produced and folded and do not fulfil their tasks? It was not until a few years ago that cell biologists began to understand the vital process of protein degradation. The organism has an important system, the ubiquitin-proteasome system, which breaks down proteins into their components in a very sophisticated way. One of the most important sites in the cell where this degradation takes place is associated with a cellular organelle, the endoplasmic reticulum (ER).

 

Newly synthesized proteins undergo a quality control process in the cell before they are sent to their respective sites of activity. This quality control system is located in the ER, a kind of distribution point in the assembly line for proteins. Proteins are folded there – the folding determines the function – and sent on down the line. “Defective goods” are sent back and receive a “molecular tag” with the protein ubiquitin. Ubiquitin, like the name implies, is present in all eukaryotic cells. As the MDC researchers have now discovered, proteins tagged as defective with ubiquitin are delivered by the protein Ubx2 to an enzyme complex (Cdc48) which transports them on to the proteasomes. Without Ubx2, the proteins cannot get there to be degraded.

 

*Ubx2 links the Cdc48 complex to ER-associated protein degradation

Oliver Neuber1, Ernst Jarosch1, Corinna Volkwein1, Jan Walter1,2 & Thomas Sommer1

1Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13092 Berlin, Germany.

2Present address: Sergievsky Center, Columbia University, 630 W 168th Street, New York, NY 10032, USA.

Correspondence should be addressed to Thomas Sommer tsommer@mdc-berlin.de

 

Barbara Bachtler

Press and Public Affairs

Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch

Robert-Rössle-Straße 10

13125 Berlin

Germany

Phone.: +49 (0) 30 94 06 - 38 96

Fax:  +49 (0) 30 94 06 - 38 33

e-mail: presse@mdc-berlin.de

http://www.mdc-berlin.de/en/news

back