Photopharmacology - A light-trigger for the proteasome

October 30, 2020

Ludwig-Maximilians-Universitaet (LMU) in Munich researchers have designed a light-sensitive inhibitor that can control cell division and cell death - and provides a promising approach for studies of essential cellular processes and the development of novel tumor therapies.

The ability to precisely control biological and chemical processes is an essential element of both basic research and medicine. Light represents an attractive stimulus in this context, as its effects can be accurately modulated both spatially and temporally. These desirable properties are the reason why the development of light-controllable molecules has become such an important goal for biological chemists. Such tools promise to make significant contributions to the elucidation of basic cellular functions, the detailed understanding of medical disorders and the design of new therapeutic strategies to combat them. A group of researchers led by cell biologist Esther Zanin at LMU's Biocenter, in cooperation with the chemist Henry Dube (who moved in April of this year from the LMU to the University of Erlangen-Nürnberg) has now developed a light-sensitive chemical inhibitor, that allows them to control two fundamental cellular processes, cell division and cell death, with light.

Cell division is a vital and highly complex process. It is therefore subject to tight regulation to ensure that cells divide only at the right time and error free. Defective cells are eliminated by programmed cell death (also known as 'apoptosis'). Both correct cell division and the disposal of defective cells depend on a molecular machine called the proteasome, which specifically degrades cellular proteins that are either damaged or no longer required.

"We have now modified an established and versatile chemical inhibitor of the proteosome by adding a light-sensitive protective group to it," says Zanin. "This group blocks the reactive aldehyde function of the inhibitor and prevents it from binding to the proteasome." In the dark, the inhibitor is therefore inactive and the proteasome functions normally. However, exposure of the cells to blue light detaches the protective group, thus allowing the inhibitor to interact with the proteosome and inhibit its function. Since the activating blue light radiation can be accurately targeted, the action of the inhibitor can be very precisely controlled. "By this means, we are able to arrest the division of tumor cells at a specific stage of the process, and to trigger apoptosis in a targeted manner," Zanin explains.

She and her colleagues believe that the new light-sensitive proteosome inhibitor will prove to be a valuable tool for the study of a wide range of dynamic cellular processes - for example, in the context of development, during which cells and tissues undergo rapid and often radical changes during a short time and at confined locations. In addition, proteosome inhibitors have promising applications as therapeutic agents - in the treatment of cancer, for instance. "The ability to activate these compounds specifically in both time and space could make them more efficacious in the future, while reducing the incidence of side-effects," says Zanin. However, reaching this goal will require further work, as the inhibitor employed in the new study is not suitable for medical use in its present form.

Ludwig-Maximilians-Universität München

Related Cell Division Articles from Brightsurf:

Cell division: Cleaning the nucleus without detergents
A team of researchers, spearheaded by the Gerlich lab at IMBA, has uncovered how cells remove unwanted components from the nucleus following mitosis.

Genetic signature boosts protein production during cell division
A research team has uncovered a genetic signature that enables cells to adapt their protein production according to their state.

Inner 'clockwork' sets the time for cell division in bacteria
Researchers at the Biozentrum of the University of Basel have discovered a 'clockwork' mechanism that controls cell division in bacteria.

Scientists detail how chromosomes reorganize after cell division
Researchers have discovered key mechanisms and structural details of a fundamental biological process--how a cell nucleus and its chromosomal material reorganizes itself after cell division.

Targeting cell division in pancreatic cancer
Study provides new evidence of synergistic effects of drugs that inhibit cell division and support for further clinical trials.

Scientists gain new insights into the mechanisms of cell division
Mitosis is the process by which the genetic information encoded on chromosomes is equally distributed to two daughter cells, a fundamental feature of all life on earth.

Cell division at high speed
When two proteins work together, this worsens the prognosis for lung cancer patients: their chances of survival are particularly poor in this case.

Cell biology: The complexity of division by two
Ludwig-Maximilians-Universitaet (LMU) in Munich researchers have identified a novel protein that plays a crucial role in the formation of the mitotic spindle, which is essential for correct segregation of a full set of chromosomes to each daughter cell during cell division.

Better together: Mitochondrial fusion supports cell division
New research from Washington University in St. Louis shows that when cells divide rapidly, their mitochondria are fused together.

Seeing is believing: Monitoring real time changes during cell division
Scientist have cast new light on the behaviour of tiny hair-like structures called cilia found on almost every cell in the body.

Read More: Cell Division News and Cell Division Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to