The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division.
In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis is greater than the overall rate of cellular degradation.
The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.
Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, with progression through the various phases of the cell cycle occurring only when favorable conditions are met. There are many checkpoints in the cell cycle, but the three major ones are: the G1 checkpoint, also known as the Start or restriction checkpoint or Major Checkpoint; the G2/M checkpoint; and the metaphase-to-anaphase transition, also known as the spindle checkpoint. Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein subunits called cyclins, different forms of which are produced at each stage of the cell cycle to control the specific events that occur therein.
Reversine, or 2-(4-morpholinoanilino)-6-cyclohexylaminopurine, is a small molecule developed by the group of Peter G. Schultz, used for stem cell dedifferentiation.
Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.
Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.
Aurora kinase inhibitors are a putative drug class for treating cancer. The Aurora kinase enzymes could be potential targets for novel small-molecule enzyme inhibitors.
Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response. Activation of Chk1 results in the initiation of cell cycle checkpoints, cell cycle arrest, DNA repair and cell death to prevent damaged cells from progressing through the cell cycle.
Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the PLK1 gene.
The cell division cycle protein 20 homolog is an essential regulator of cell division that is encoded by the CDC20 gene in humans. To the best of current knowledge its most important function is to activate the anaphase promoting complex (APC/C), a large 11-13 subunit complex that initiates chromatid separation and entrance into anaphase. The APC/CCdc20 protein complex has two main downstream targets. Firstly, it targets securin for destruction, enabling the eventual destruction of cohesin and thus sister chromatid separation. It also targets S and M-phase (S/M) cyclins for destruction, which inactivates S/M cyclin-dependent kinases (Cdks) and allows the cell to exit from mitosis. A closely related protein, Cdc20homologue-1 (Cdh1) plays a complementary role in the cell cycle.
WEE1 homolog , also known as WEE1, is a protein which in humans is encoded by the WEE1 gene.
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene. Also known as BubR1, this protein is recognized for its mitotic roles in the spindle assembly checkpoint (SAC) and kinetochore-microtubule interactions that facilitate chromosome migration and alignment. BubR1 promotes mitotic fidelity and protects against aneuploidy by ensuring proper chromosome segregation between daughter cells. BubR1 is proposed to prevent tumorigenesis.
Aurora kinase C, also Serine/threonine-protein kinase 13 is an enzyme that in humans is encoded by the AURKC gene.
Mitotic Catastrophe has been defined as either a cellular mechanism to prevent potentially cancerous cells from proliferating or as a mode of cellular death that occurs following improper cell cycle progression or entrance. Mitotic catastrophe can be induced by prolonged activation of the spindle assembly checkpoint, errors in mitosis, or DNA damage and functioned to prevent genomic instability. It is a mechanism that is being researched as a potential therapeutic target in cancers, and numerous approved therapeutics induce mitotic catastrophe.
BI 811283 is a small molecule inhibitor of the Aurora B kinase protein being developed by Boehringer Ingelheim for use as an anti-cancer agent. BI 811283 is currently in the early stages of clinical development and is undergoing first in human trials in patients with solid tumors and acute myeloid leukemia.
Multipolar spindles are spindle formations characteristic of cancer cells. Spindle formation is mostly conducted by the aster of the centrosome which it forms around itself. In a mitotic cell wherever two asters convene the formation of a spindle occurs.
Kinesin-like protein KIF11 is a molecular motor protein that is essential in mitosis. In humans it is coded for by the gene KIF11. Kinesin-like protein KIF11 is a member of the kinesin superfamily, which are nanomotors that move along microtubule tracks in the cell. Named from studies in the early days of discovery, it is also known as Kinesin-5, or as BimC, Eg5 or N-2, based on the founding members of this kinesin family.
Andrea Musacchio is an Italian structural biologist. He is Max Planck director at the Institute of Molecular Physiology in Dortmund. He is also Honorary Professor at the Center for Medical Biotechnology at the University of Duisburg-Essen. He was named European Molecular Biology Organization member in 2009.
