CAK Activation Of Plant Cell Cycle: Scientists Find Another Piece In The Jigsaw Puzzle To Help Explain Why Plants Do Not Develop Cancer Spontaneously

May 08, 1998

Cancer cells proliferate uncontrolled, so regulation of the entry into the cell division cycle by external hormonal and stress stimuli is a central theme of cancer research. In contrast to animals, plants appear to have strong preventive mechanisms to avoid this kind of uncontrolled cell division. On the other hand, and unlike animal cells, plant cells that fulfill specific functions and are therefore differentiated are able to reactivate cell division. This is the reason why it is possible to regenerate new plants from individual cells in tissue culture. However, because of the differences between plants and animals, the identification of functions regulating the plant cell cycle may provide an important lesson about how evolutionary changes have led to less rigorous control of cell proliferation in mammals.

In all eukaryotes, the cell cycle is regulated by enzymes called cyclin-dependent protein kinases (CDKs). Plants harbour several different CDKs that are all related to their yeast and animal counterpart. Activation of the cell cycle at various control points requires the phosphorylation of CDKs by CDK-activating kinases (CAKs) that represent important targets within cellular signaling pathways. Two major types of CAKs have so far been identified. One type establishes contact with the machinery necessary to provide the template (messenger RNA) to produce proteins within a cell according to the DNA blueprint. This machinery is called the transcriptional apparatus and contains an enzyme called RNA polymerase II complex, which is necessary to produce the messenger RNA. These CAKs, known from animals and fission yeasts, make contact to a particular part of a subunit of the RNA polymerase II complex. The activity of this part of the subunit plays a role in the regulation of the interaction of the RNA polymerase with proteins that regulate transcription.

In contrast, other types of CAK either cannot bind the RNA polymerase or are subunits of the RNA polymerase II complex and cannot phosphorylate the cyclin-dependent-kinase. This phosphorylation is necessary for cell proliferation.

CAKs thus seem to perform important functions throughout the life of a cell since they appear to be implicated in the control of both the cell cycle and transcription, as well as DNA repair, where they perform a distinct function, controlling carcinogenesis. Scientist are eager to find out how plant cells control the activation of their division, and how this differs in animals. The first significant step has now been made: Dr. Masaaki Umeda's laboratory at Tokyo University, Japan, collaborating with Dr. Csaba Koncz's laboratory in the department of Jeff Schell at the Max Planck Institute for Plant Breeding Research (Max-Planck-Institut für Züchtungsforschung) in Köln, Germany, reported recently in PNAS (Vol. 95, Issue 9, 5021-5062, April 28, 1998) the identification of the first functionally characterised plant CAK.

Using gene technology they transferred copies of many different genes (cDNA) from arabidopsis, a common weed, into budding yeast mutants that had a defect in genes responsible for the production of yeast CAKs. In this way they could complement the budding yeast mutations with arabidopsis genes and identify a plant CAK gene. Remarkably, the plant CAK can fully replace the function of RNA polymerase II-binding cell-cycle-activating kinases in both fission yeast and budding yeasts, and can phosphorylate and activate the human cell-cycle kinase CDK2. However the arabidopsis CAK is not able to recognize the C-terminal domain of RNA polymerase II, which is necessary for the production of messenger RNA (basal transcription). The newly identified plant CAK thus performs a novel type of intermediate function which may highlight some important differences between the mechanisms regulating cell division in fungi, plants, and animals.


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