Scientists in Cologne identify important lysine-acetylation regulatory mechanisms for Ran protein

Discoveries made by scientists in Cologne lead to new perspectives in the treatment of colorectal cancer, lung cancer, and lymphomas. Dr. Michael Lammers and his research team at CECAD have identified new regulatory mechanisms for Ran protein.

They have shown that all essential functions of the small GTP-binding Ran protein can be regulated by lysine acetylation. Ran is involved in many important cell processes including cell division and protein transport. Dysregulation of these processes has dramatic effects on normal cell development.

Many types of tumor cells have increased concentrations of Ran or Ran-interacting proteins or Ran-regulators. Switching off Ran-function in a targeted manner, using the newly identified regulatory system, may provide novel therapeutic approaches.

The small Ran protein is a molecular switch that can be turned on or off depending on the nucleotide charge. If this switch protein is not regulated properly, there may be far-reaching effects on essential cell functions.

Using high-resolution quantitative mass spectrometry, it has recently been shown that many of many of the amino acids – the lysines – in the Ran protein can be modified by adding an acetyl group. Modifications of this type made to the folded protein, once biosynthesis is complete, essentially alter and regulate protein function. Some of the acetylation sites are to be found in highly relevant functional regions within the Ran protein.

Dr. Lammers: “With a combined synthetic biological, biochemical, and cell biological approach, we have shown that lysine acetylation regulates nearly all essential Ran functions – something that was completely unknown beforehand. For some of the sites, we have also been successful in identifying specific enzymes responsible to modify the protein in this way, adding and removing such modifications. These findings may allow us to develop novel agents for cancer therapy.”

Cancer is the second most common cause of death in industrialized nations and responsible for about 25% of all deaths. The risk of malignancy increases with age – which means that research into the development and treatment of cancer is of great economic and personal interest in an aging society. CECAD, the Cluster of Excellence at the University of Cologne, is carrying out research into aging and its associated diseases. CECAD’s vision is to develop new treatments for the entire spectrum of age-related diseases. Given this aim, the latest findings from Dr. Lammers and his team are of great import.

Published in: Proc. Natl. Acad. Sci. U. S. A.; on June 29th 2015 (Epub)

de Boor, S.*, Knyphausen, P.*, Kuhlmann, N., Wroblowski, S., Brenig, J., Nolte, H., Krüger, M., and Lammers, M. (2015). Small GTP-binding protein Ran is regulated by posttranslational lysine-acetylation. Proc. Natl. Acad. Sci. U. S. A.] 12(28):E3679-88. doi: 10.1073/pnas.1505995112. Epub 2015 Jun 29.
*(contributed equally to the work)

Contact:
Dr. Michael Lammers
mlammers@uni-koeln.de
Tel. +49(0) 221-478-84308/84314

Astrid Bergmeister MBA
Head of PR & Marketing, CECAD
University of Cologne
Phone: +49 (0)221 478 84043
Email: astrid.bergmeister@uk-koeln.de

http://cecad.uni-koeln.de

Media Contact

Astrid Bergmeister idw - Informationsdienst Wissenschaft

All latest news from the category: Life Sciences and Chemistry

Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to home

Comments (0)

Write a comment

Newest articles

Lighting up the future

New multidisciplinary research from the University of St Andrews could lead to more efficient televisions, computer screens and lighting. Researchers at the Organic Semiconductor Centre in the School of Physics and…

Researchers crack sugarcane’s complex genetic code

Sweet success: Scientists created a highly accurate reference genome for one of the most important modern crops and found a rare example of how genes confer disease resistance in plants….

Evolution of the most powerful ocean current on Earth

The Antarctic Circumpolar Current plays an important part in global overturning circulation, the exchange of heat and CO2 between the ocean and atmosphere, and the stability of Antarctica’s ice sheets….

Partners & Sponsors