The error-free distribution of genetic material during cell division is important for preventing the development of tumor cells. Prof. Erich Nigg’s research group at the Biozentrum, University of Basel, has uncovered a new important function of the human enzyme Plk1. It plays a significant role in monitoring chromosome segregation. The results published in the journal "Cell Reports" may provide important clues for the treatment of cancer.
Each day, the cells of the human body divide billions of times; this also requires duplication of their genetic information. Errors in cell division can cause tumor formation, and an exact segregation of the DNA (chromosomes) is therefore essential to ensure the health of the whole organism.
Prof. Erich Nigg’s research group at the Biozentrum, University of Basel, has demonstrated that the enzyme Plk1 plays a significant role in monitoring the segregation of chromosomes.
Plk1 has checkpoint function
The segregation of the 23 chromosome pairs of human cells only occurs when all parameters are correct. This is ensured by a surveillance process, a so-called checkpoint. Central to this checkpoint is an inhibitor formed on the chromosomes, called mitotic checkpoint complex (MCC), which prevents cell division until all settings on the mitotic spindle, the chromosome segregation apparatus, are correct.
“Just like the enzyme Mps1, Plk1 also ensures the assembly of the MCC and finally the inhibition of cell division,” says the first author Conrad von Schubert. “Plk1 thus also has a checkpoint function and consequently safeguards chromosome segregation.”
In the past, various functions have been attributed to the enzyme Plk1, including the correct assembly and disassembly of the mitotic spindle. “The newly uncovered checkpoint function of Plk1 had been overlooked, however, since other functions obscured this phenomenon,” explains Conrad von Schubert.
The research team could now demonstrate that Plk1 influences the inhibitor MCC via at least two pathways. In a nutshell, Plk1 supports the enzyme Mps1, whose checkpoint function had already been known for some time. “Plk1 ensures rapid and robust checkpoint activation by acting in a similar way to Mps1, thus reinforcing Mps1 activity,” says Conrad von Schubert.
Plk1 demonstrates evolutionary stability
“While Plk1 and Mps1 cooperate in human cells, Plk1 has prevailed over Mps1 during the evolution of other organisms,” remarks Conrad von Schubert. Because Mps1 has disappeared in the nematode Caenorhabditis elegans, Plk1 has taken over the entire checkpoint function in this organism, as shown by an independent study in the same issue of the journal.
Combined drugs against cancer?
Mps1 is currently being investigated as a possible target for the treatment of cancer. “However, the fact that Plk1 also exhibits checkpoint function during cell division was not known,” says Conrad von Schubert. The new findings suggest that both enzymes should be considered as targets for cancer therapy. “Drugs against Plk1 were developed some time ago and, in light of our findings, it would be interesting to test the potential of a combinatorial treatment.”
Conrad von Schubert, Fabien Cubizolles, Jasmine M. Bracher, Tale Sliedrecht, Geert J.P.L. Kops, and Erich A. Nigg
Plk1 and Mps1 Cooperatively Regulate the Spindle Assembly Checkpoint in Human Cells
Cell Reports, published online June 25, 2015, doi: 10.1016/j.celrep.2015.06.007
Prof. Dr. Erich Nigg, University of Basel, Biozentrum, phone: +41 61 267 16 56, email: firstname.lastname@example.org
Olivia Poisson | Universität Basel
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research