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Basic plant research provides insights into cancer research

Claus Schwechheimer’s work group at the Centre for Plant Molecular Biology at the University of Tübingen has succeeded in identifying a protein function in plants, which, if it is understood, might lead to important progress in human cancer research.

In all organisms, the controlled degradation of proteins in their cells is as important as their production: faulty or incomplete protein degradation often leads to cellular dysfunctions or even to cell death. The machinery that controls these degradation processes is similar in all organisms – plants, animals and humans. A protein complex known as COP9 signalosome regulates the activity of E3 lipases, which are essential for the targeted degradation of proteins through another protein complex.
Prof. Dr. Claus Schwechheimer – head of a research group at the Centre for Plant Molecular Biology (ZMBP) at the University of Tübingen. (Photo: ZMBP, University of Tübingen)
A reduced number of signalosomes in the cells leads to massive disturbances of the E3 ligase function, and as a result leads to an increase in dysfunctions that might cause uncontrolled cell division (tumours) or cell death.

The COP9 signalosome is responsible for many cellular processes and controls a large number of E3 ligases and hence the degradation of a large number of regulatory proteins. It would appear to be difficult for a single researcher to be able to clarify all the feedback loops. However, using state-of-the-art technology, Schwechheimer has now succeeded in gaining important insights from the large number of feedback loops into the potential defects of a mechanism that controls cell division.

Cell division is an important process in the growth of an organism: ”[..] but the DNA has to be transferred from the mother cell to the daughter cells whole and unaltered – faulty transfer of DNA almost inevitably leads to disease or death,” explained the scientist. Therefore, cells have developed sophisticated mechanisms to help them to minimise the number of mistakes occurring as well as developing mechanisms to repair mistakes should they occur.

Protein functions in plant cells that are of importance for cancer research

Indeed, Schwechheimer and his team have succeeded in showing that plant cells with defective signalosomes doubled their DNA at the same time as stopping the actual division process because the DNA was damaged. Since this prevents growth, the cell remains in an incomplete division phase. Schwechheimer now assumes that the E3 ligases, which repair DNA damage, no longer function properly if the signalosome is damaged or is missing altogether. That means that Schwechheimer has discovered the connection between defective signalosomes and vital cell functions. “It was rather like looking for a needle in a haystack; and we were extremely lucky,” admitted Schwechheimer.
Visible under the microscope: blue spots in the germinal seeds of experimental plants show the cells that contain defective genes. (Photo: ZMBP – University of Tübingen)
Visible under the microscope: blue spots in the germinal seeds of experimental plants show the cells that contain defective genes. (Photo: ZMBP – University of Tübingen)
This vital repair mechanism is not restricted to plant cells; animal and human cells also rely on the faultless replication of DNA and cell division. Otherwise, malfunctions would occur that in many cases result in cancer. “It is very likely that we have discovered a mechanism that is also important for the repair of DNA in our body cells; therefore, there is most likely a close connection with the onset of cancer,” said Schwechheimer.

The researchers will now have to undertake further research into the signalosome’s role in human cells and the onset of cancer. Schwechheimer is hoping to discuss the findings with colleagues from the field of medical research.

Schwechheimer has set himself clear goals for his own research on plant cells: “We have found a universal cell mechanism that can easily be investigated in plant cells without posing a risk to human health. However, we still lack a few important details. We are working hard to clarify these details in order to be able to influence these cellular processes in the future.”

Esther M.N. Dohmann, Mitchell P. Levesque, Lieven De Veylder, Ilka Reichardt, Gerd Jürgens, Markus Schmid, and Claus Schwechheimer (2008). The Arabidopsis COP9 signalosome is essential for G2 phase progression and genomic stability. Development 135, 2013 - 2022.

Source: ZMBP - 15th July 2008
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/basic-plant-research-provides-insights-into-cancer-research