THE HUMAN PROTEIN ATLAS BLOG
Image of the week - the cell cycle and mitosis
It's time for another Image of the week! This week's image is brought to us by Diana Mahdessian, who works on the Subcellular protein atlas, and highlights cell division and various stages of mitosis. In previous blogs we have discussed the importance of certain proteins in the cell cycle including dividing centrosomes and FDXR in mitochondria.
The cell cycle is an ordered series of events that ultimately leads to the division of the "mother" cell into two "daughter" cells (cells are given feminine names because they are capable of reproducing).
The cell cycle consists of three distinct phases; interphase, mitosis and cytokinesis. During interphase the cell grows and duplicates its DNA. This is where the cell spends most of its time (about 1 day) before eventually dividing into two daughter cells during mitosis. The whole process of mitosis, the segregation of chromosomes into two daughter cells occurs very rapidly, taking only roughly 30 minutes. The final stage of cell division, cytokinesis occurs when the cytoplasm of the two daughter cells is completely separated, this takes roughly an hour (60 minutes). The mitotic phase is the shortest phase of the cell cycle yet it is the most crucial as disfunction in this process can lead severe disorders including missing chromosomes and improperly formed nuclei.
Mitosis itself consists of five phases: prophase, prometaphase, metaphase, anaphase and telophase. The cells seen in Figure 1 are selected to be representative of those seen in the Subcellular HPA as a cell progresses through the phases of mitosis. The various phases of the cell cycle and mitosis are labeled in a clockwise fashion. As a reference for the terms discussed below, Figure 2 from Walczak C.E. et al. 2010 shows a labeled schematic of cell division.
During prophase the chromosomes within the nucleus condense and become more compact as the mitotic spindle assembles between the two centrosomes. Next, the cell enters prometaphase where the nuclear membrane breaks down into small vesicles and chromosomes attach to the microtubules at their kinetochore. When metaphase begins the chromosomes align along the center of the cell called the "metaphase plate" or the "cell equator" and the assembly of the spindle is now complete. Once aligned, chromosome separation can occur as each sister copy of a chromosome's (chromatid) is pulled toward opposite kinetochores. Finally, during Telophase the chromosomes arrive at the cell poles where the nuclear membrane is reformed around each set of chromosomes (O'Connor et al. 2008).
An example of a known cell cycle dependent protein is cyclin B1. It is a member of the cyclin family, and it is essential to trigger mitosis. Cyclin B1 accumulates in the cytoplasm through the cell cycle and shuttles to the nucleus at Prophase (Pines et al. 1991, Gavet et al. 2010). Confocal images of cyclin B1 in the HPA show this variation in the abundance of the protein in the cytoplasm.
The cell cycle and cell division is the most crucial task your cells perform. Without any division, you would die within days ( Molecular Biology of the Cell, 5th edition). The diseases associated with abnormal cell cycle progression are too numerous to list, but include all cancers, neurodegenerative disorders, autoimmune disorders, and premature aging to name a few (Zhivotovsky B. & Orrenius S. 2010). As a result, in the HPA we are working to characterize the cell cycle dependency of the entire human proteome. Eventually we hope this work will help us understand how aberrations in the expression of cell cycle regulators leads to proliferative diseases.
By the end of this year the HPA, we will release data about cell cycle dependent proteins expression variation, either by abundance or spatial redistribution.
We would like to thank all the members of the Subcellular Human Protein Atlas who generate these images and especially to Diana Mahdessian for contributing this article about the cell cycle.