Cell cycle control in plants

The basic unit of life is a cell and all organisms are either one-cellular, such as bacteria and yeast, or multicellular, such as animals and plants. Another basic property shared by all organisms is their ability to reproduce themselves. This process relies on the fact that cells can duplicate the genetic information contained in their chromosomal DNA before equal distribution to the daughter cells in mitosis. The process of cellular duplication and division is called the cell cycle and consists of a series of complex steps that have to be coordinated in time and space. The importance of cell cycle regulation is shown by the fact that misregulation can result in either cell death or tumour formation. About ten years ago, it became clear that yeasts, animals, and humans share a very similar molecular machinery for cell cycle regulation. The principal regulator turned out to be CDK (cyclin-dependent kinase) that functions as a molecular switch dictating a cell when to divide. CDK does this by phosphorylating and thereby activating several important proteins, including those that package and distribute DNA. The team of Prof. Hirt identified the molecular components of the plant cell cycle machinery. In 1991, the group isolated a plant CDK and showed that baker`s yeast cells that suffer from a lethal mutation in the yeast CDK gene can be rescued by the plant CDK, demonstrating that the cell cycle regulators belong to the most highly conserved genes in evolution. Being the central regulator to tell a cell to divide or not to divide, a CDK is held inactive in the cell for most of its time and activation of a CDK only occurs when a positive regulator, a so-called cyclin, is produced by the cell. Cyclins derive their name from their short-lived cyclic appearance during the life cycle of a cell. Prof. Hirt`s group was among the first to identify cyclins in plants showing that cyclins activate CDK at specific steps in the cell cycle in response to specific extracellular signals. As work on the cell cycle proceeded, it became clear that a CDK is not only regulated by cyclins but also by other protein kinases and phosphatases, enzymes that either add or remove phosphate residues from certain amino acid residues of a CDK. The identified protein kinases and phosphatases were found to be important conveyers of extracellular signals that either promote or inhibit cell division. Favorable signals, such as growth factors and nutrients activate a CDK, whereby unfavorable conditions, such as irradiation or DNA damaging substances, inhibit a CDK and thereby stop cell cycle progression. During the last decade, the Hirt group isolated a range of different protein kinases and phosphatases and analyzed their role in the cell division process. Several kinases and phosphatases were identified that mediate intracellular signaling of a number of environmental factors, including dehydration, high salt, or pathogen attack. Because abiotic stresses, pathogen attack and cell cycle cues are transmitted through many of the same signaling pathways, it became obvious that cells don`t process information via linear but through parallel and highly interactive signaling chains. Thinking along these lines, a consortium of European labs headed by Prof. Hirt was recently approved to take a multidisciplinary approach to analyze integration, branching and cross talk between different pathways in response to different stimuli. The European groups will use newly developed techniques of genomics, proteomics, and apply new computer algorithms for modeling of the signaling processes. Because intracellular signaling pathways have similarity to neuronal networks, this research might also help to solve complex problems in other fields of science.

The basic unit of life is a cell and all organisms are either one-cellular, such as bacteria and yeast, or multicellular, such as animals and plants. Another basic property shared by all organisms is their ability to reproduce themselves. This process relies on the fact that cells can duplicate the genetic information contained in their chromosomal DNA before equal distribution to the daughter cells in mitosis. The process of cellular duplication and division is called the cell cycle and consists of a series of complex steps that have to be coordinated in time and space. The importance of cell cycle regulation is shown by the fact that misregulation can result in either cell death or tumour formation. About ten years ago, it became clear that yeasts, animals, and humans share a very similar molecular machinery for cell cycle regulation. The principal regulator turned out to be CDK (cyclin-dependent kinase) that functions as a molecular switch dictating a cell when to divide. CDK does this by phosphorylating and thereby activating several important proteins, including those that package and distribute DNA. The team of Prof. Hirt identified the molecular components of the plant cell cycle machinery. In 1991, the group isolated a plant CDK and showed that baker`s yeast cells that suffer from a lethal mutation in the yeast CDK gene can be rescued by the plant CDK, demonstrating that the cell cycle regulators belong to the most highly conserved genes in evolution. Being the central regulator to tell a cell to divide or not to divide, a CDK is held inactive in the cell for most of its time and activation of a CDK only occurs when a positive regulator, a so-called cyclin, is produced by the cell. Cyclins derive their name from their short-lived cyclic appearance during the life cycle of a cell. Prof. Hirt`s group was among the first to identify cyclins in plants showing that cyclins activate CDK at specific steps in the cell cycle in response to specific extracellular signals. As work on the cell cycle proceeded, it became clear that a CDK is not only regulated by cyclins but also by other protein kinases and phosphatases, enzymes that either add or remove phosphate residues from certain amino acid residues of a CDK. The identified protein kinases and phosphatases were found to be important conveyers of extracellular signals that either promote or inhibit cell division. Favorable signals, such as growth factors and nutrients activate a CDK, whereby unfavorable conditions, such as irradiation or DNA damaging substances, inhibit a CDK and thereby stop cell cycle progression. During the last decade, the Hirt group isolated a range of different protein kinases and phosphatases and analyzed their role in the cell division process. Several kinases and phosphatases were identified that mediate intracellular signaling of a number of environmental factors, including dehydration, high salt, or pathogen attack. Because abiotic stresses, pathogen attack and cell cycle cues are transmitted through many of the same signaling pathways, it became obvious that cells don`t process information via linear but through parallel and highly interactive signaling chains. Thinking along these lines, a consortium of European labs headed by Prof. Hirt was recently approved to take a multidisciplinary approach to analyze integration, branching and cross talk between different pathways in response to different stimuli. The European groups will use newly developed techniques of genomics, proteomics, and apply new computer algorithms for modeling of the signaling processes. Because intracellular signaling pathways have similarity to neuronal networks, this research might also help to solve complex problems in other fields of science.