STOPAPCG1IMP · Spatial-temporal regulation of APC/C, its role on G1 arrest and impact on terminal differentiation

Spatial-temporal regulation of APC/C, its role on G1 arrest and impact on terminal differentiation

Cells are the basic building blocks for living organisms, including us, humans. For an organism to grow and develop into adult forms, cells need to duplicate through a coordinated process called “cell cycle”. Through this process, a single mother cell divides to generate two genetically identical daughter cells. After division, cells need to respond to external cues from the surrounding tissue and decide whether to continue dividing or to halt the cell cycle to become specialised in a task required for the proper function of the tissue/organ where they reside. The right balance between these two fates of cells is essential not only for forming proper shapes of organs and tissues but also for maintaining their functions throughout the life of the organisms. When this balance is perturbed, cells may continue dividing uncontrollably, leading to tumorigenesis. Alternatively, all the cells may become specialised and stop producing new cells, which accelerates the degeneration of tissues or the ageing process. Therefore, understanding how the division of the cells, i.e., the cell cycle, is coordinated with their responses to the external clues is key to understanding the causes of the formation and progression of tumours as well as the pathology of degenerative disorders, which will ultimately help develop new therapeutic strategies to these diseases. To control the cell cycle, the cell has several effectors composed of proteins, collectively called “cell cycle regulators”. The levels of these players within the cell are controlled through production and destruction. One of the critical factors for the control of the protein levels during the cell cycle is the Anaphase Promoting Complex/Cyclosome (APC/C). This complex recognises proteins with specific signatures (or degrons) and targets them for degradation via the protein destruction machinery called the proteasome. Accumulating evidence suggests that the APC/C is involved in the control of the balance between cell division and specialisation, however, the knowledge about how the APC/C accomplishes such a task remains scarce. In this project, I aimed to understand how the APC/C coordinates the cell cycle with the cell specialisation process using the fruit fly, Drosophila melanogaster, as a model organism. During the natural developmental process of Drosophila, the developing eye shows a remarkable, tight coordination between cell proliferation and the steps for cell specialisation. I took full advantage of this unique feature to investigate the role of the APC/C in the coordination between cell cycle and specialisation. The majority of cell cycle regulators, including APC/C, as well as the genes regulating cells’ responses to external cues, are very similar between Drosophila and mammals, although the genetic circuit in Drosophila is relatively simple and less complex compared to mammals. Therefore, using the fruit fly allows us to faster and more easily obtain results that are likely to be applicable to mammals.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз