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
Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
20.11.2018 | Life Sciences
20.11.2018 | Life Sciences
20.11.2018 | Physics and Astronomy