PROTEIN PHOSPHATASE 1 (PP1) IN THE REGULATION OF MITOTIC EXIT AND NUCLEAR ORGANISATION

点击翻译按钮获取中文摘要

The important information that is responsible for the successful reproduction and development of an organism is packaged within cells and must be passed on correctly to the next generation of cells. This passing on the information is referred to as cell division and is called mitosis. In humans, a fertilized single-celled egg requires many cell divisions to make a new individual. In an adult, nerve and muscle cells do not divide but liver cells divide once a year. More than one division a day occurs in blood cell precursors in the bone marrow and in the cells lining the gut. Therefore our survival requires a production of millions of cells daily. Mitosis is an extremely important phase in the life of any cell and it must be carried out without errors. If a cell division goes wrong then major consequences may arise either for the cell or for future generations. Mitotic errors during development can produce malformations or miscarriages and, in adults they can lead to cancer. The proposed research is looking at the proteins that regulate the final steps of mitotic divisions. Proteins can have extremely specialised functions. Some are important for building structures while others are involved in chemical reactions occurring within a cell. One family of such proteins with chemical functions is called phosphatases and they are involved in many important cell reactions. Among them is Protein phosphatase 1 (PP1). My previous research has shown that PP1 together with a partner protein Repo-Man is very important for controlling cell division and their malfunction leads to dramatic problems in the cell progeny. In particular, they produce derivative cells that manifest mistakes in the organization of the genomic material and the Nuclear Lamina (an important barrier that enclose the genomic material in a cell). These defects are similar to the ones that occur in cancer cells and in cells during the aging process. It is therefore imperative to acquire more in depth knowledge on how PP1 works and why its malfunction affects the outcome of cell division. The proposal is to gain a better understanding of how this PP1 contributes to the regulation of cell division, what are the consequences to the cell should this process go wrong and also to identify new proteins that are important for PP1 activity. Finally, obtaining a highly detailed description of how these molecules work together will provide the background mean to generate chemicals that can act by modulating their action and therefore could be used to control cell division in pathological cases.