The Kinesin 8 Family are a subfamily of the molecular motor proteins known as kinesins. Most kinesins transport materials or cargo around the cell while traversing along microtubule polymer tracks with the help of ATP-hydrolysis-created energy. The Kinesin 8 family has been shown to play an important role in chromosome alignment during mitosis. Kinesin 8 family members KIF18A in humans [1] and Kip3 in yeast [2] have been shown to be in vivo plus-end directed microtubule depolymerizers. During prometaphase of mitosis, the microtubules attach to the kinetochores of sister chromatids. Kinesin 8 is thought to play some role in this process, as knockdown of this protein via siRNA produces a phenotype of sister chromatids that are unable to align properly. [1] [3]
In cell biology, mitosis is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division gives rise to genetically identical cells in which the total number of chromosomes is maintained. In general, mitosis is preceded by the S stage of interphase and is often followed by telophase and cytokinesis; which divides the cytoplasm, organelles and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of Mitosis all together define the mitotic (M) phase of an animal cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can grow as long as 50 micrometres and are highly dynamic. The outer diameter of a microtubule is between 23 and 27 nm while the inner diameter is between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.
Anaphase, is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes are moved to opposite poles of the cell. Chromosomes also reach their overall maximum condensation in late anaphase, to help chromosome segregation and the re-formation of the nucleus.
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.
Telophase is the final stage in both meiosis and mitosis in a eukaryotic cell. During telophase, the effects of prophase and prometaphase are reversed. As chromosomes reach the cell poles, a nuclear envelope is re-assembled around each set of chromatids, the nucleoli reappear, and chromosomes begin to decondense back into the expanded chromatin that is present during interphase. The mitotic spindle is disassembled and remaining spindle microtubules are depolymerized. Telophase accounts for approximately 2% of the cell cycle's duration.
The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), 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.
A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. Its proteins also help to hold the sister chromatids together and play a role in chromosome editing. Details of the specific areas of origin are unknown.
The Kinesin-13 Family are a subfamily of motor proteins known as kinesins. Most kinesins transport materials or cargo around the cell while traversing along microtubule polymer tracks with the help of ATP-hydrolysis-created energy.
Mad2 is an essential spindle checkpoint protein. The spindle checkpoint system is a regulatory system that restrains progression through the metaphase-to-anaphase transition. The Mad2 gene was first identified in the yeast S. cerevisiae in a screen for genes which when mutated would confer sensitivity to microtubule poisons. The human orthologues of Mad2 were first cloned in a search for human cDNAs that would rescue the microtubule poison-sensitivity of a yeast strain in which a kinetochore binding protein was missing. The protein was shown to be present at unattached kinetochores and antibody inhibition studies demonstrated it was essential to execute a block in the metaphase-to-anaphase transition in response to the microtubule poison nocodazole. Subsequent cloning of the Xenopus laevis orthologue, facilitated by the sharing of the human sequence, allowed for the characterization of the mitotic checkpoint in egg extracts.
Aurora B kinase is a protein that functions in the attachment of the mitotic spindle to the centromere.
Polo-like kinases (Plks) are regulatory serine/threonin kinases of the cell cycle involved in mitotic entry, mitotic exit, spindle formation, cytokinesis, and meiosis. Only one Plk is found in the genomes of fruit flies (Polo), budding yeast (Cdc5) and fission yeast (Plo1). Vertebrates, however, have many Plk family members including Plk1, Plk2/Snk, Plk3/Prk/FnK, Plk4/Sak and Plk5. Of the vertebrate Plk family members, the mammalian Plk1 has been most extensively studied. During mitosis and cytokinesis, Plks associate with several structures including the centrosome, kinetochores, and the central spindle.
Kinesin-like protein KIF23 is a protein that in humans is encoded by the KIF23 gene.
Centromere-associated protein E is a protein that in humans is encoded by the CENPE gene.
Kinesin-like protein KIF22 is a protein that in humans is encoded by the KIF22 gene.
Kinesin-like protein KIF2C is a protein that in humans is encoded by the KIF2C gene.
Kinesin-like protein KIF3A is a protein that in humans is encoded by the KIF3A gene.
KIF1-binding protein, also known as Kinesin binding protein(KBP), is a protein that in humans is encoded by the KIAA1279 gene. The interaction of KBP with Kif15 is necessary for the localization of Kif15 to the microtubule plus-end at the spindle equator. Interaction between Kif15 and KBP is essential for the perfect alignment of chromosomes at the metaphase plate, and any defect in their interaction leads to delay in chromosomal alignment during mitosis. Anything that perturb the interaction of KBP and Kif15 can block the cells at mitosis, and hence it can be therapeutically used to control Kif15 upregulated cancer cells.
Kinesin-like protein KIF2A is a protein that in humans is encoded by the KIF2A gene.
Kinesin-5 is a molecular motor protein that is essential in mitosis. Kinesin-5 proteins are members of 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 family member 11, encoded by the KIF11 gene, or as BimC, Eg5 or N-2, based on the founding members of this kinesin family. The term kinesin-5 has been recommended based on a standardized nomenclature adopted by the scientific community.
Kinesin family member 15 is a protein that in humans is encoded by the KIF15 gene.