Kinesin-5
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Kinesin-5
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. Currently, there are over 70 different eukaryotic kinesin-5 proteins identified by sequence similarity. Members of this protein family are known to be involved in various kinds of spindle dynamics and essential for mitosis. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. The human kinesin-5 protein has been actively studied for its role in mitosis and its potential as a therapeutic target for cancer. Function KIF11 (also known as kinesin-5 and Eg5) is a h ...
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Kif11 Wiki Movie
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. Currently, there are over 70 different eukaryotic kinesin-5 proteins identified by sequence similarity. Members of this protein family are known to be involved in various kinds of spindle dynamics and essential for mitosis. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. The human kinesin-5 protein has been actively studied for its role in mitosis and its potential as a therapeutic target for cancer. Function KIF11 (also known as kinesin-5 and Eg5) is a h ...
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Kinesin Superfamily
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzyme). The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular cargo, such as in axonal transport, and intraflagellar transport. Most kinesins walk towards the plus end of a microtubule, which, in most cells, entails transporting cargo such as protein and membrane components from the center of the cell towards the periphery. This form of transport is known as anterograde transport. In contrast, dyneins are motor proteins that move toward the minus end of a microtubule in retrograde transport. Discovery Kinesins were discovered in 1985, based on their motility in cytoplasm extruded from the giant axon of the squid. They turned out as MT-based anterograde intracellular t ...
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Molecular Motor
Molecular motors are natural (biological) or artificial molecular machines that are the essential agents of movement in living organisms. In general terms, a motor is a device that consumes energy in one form and converts it into motion or mechanical work; for example, many protein-based molecular motors harness the chemical free energy released by the hydrolysis of ATP in order to perform mechanical work. In terms of energetic efficiency, this type of motor can be superior to currently available man-made motors. One important difference between molecular motors and macroscopic motors is that molecular motors operate in the thermal bath, an environment in which the fluctuations due to thermal noise are significant. Examples Some examples of biologically important molecular motors: * Cytoskeletal motors ** Myosins are responsible for muscle contraction, intracellular cargo transport, and producing cellular tension. ** Kinesin moves cargo inside cells away from the nucleus ...
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Dynactin
Dynactin is a 23 Protein subunit, subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (ACTR1A, Arp1). Discovery Dynactin was identified as an activity that allowed purified cytoplasmic dynein to move membrane vesicles along microtubules in vitro. It was shown to be a multiprotein complex and named "dynactin" because of its role in dynein activation. The main features of dynactin were visualized by quick-freeze, deep-etch, rotary shadow electron microscopy. It appears as a short filament, 37-nm in length, which resembles F-actin, plus a thinner, laterally oriented arm. Antibody labelling was used to map the location of the dynactin subunits. Structure Dynactin consists of three major structural domains: (1) sidearm-shoulder: DCTN1/p150Glued, DCTN2/p50/dynamitin, DCTN3/p24/p22;(2)the Arp1 filament: ACTR1A/Arp1/centractin, actin, CapZ; and (3) the pointed end complex: Acti ...
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Filanesib
Filanesib (code name ARRY-520) is a kinesin spindle protein (KIF11) inhibitor which has recently been proposed as a cancer treatment, specifically for multiple myeloma. History of research In 2009, two in vitro studies on the effects of filanesib on either ovarian cancer cells or acute myeloid leukemia cells were published. The former reported that filanesib "...has similar anti-tumor activity in EOC pithelial ovarian cancercells as that of paclitaxel. However, unlike paclitaxel, it does not induce these pro-tumor effects in Type I cells." The detrimental effects attributed to paclitaxel were alleged to be "...due to paclitaxel-induced enhancement of NF-κB and ERK activities, and cytokine production (e.g. IL-6), which promote chemoresistance and tumor progression." The latter study also reported promising results, concluding that filanesib "...potently induces cell cycle block and subsequent death in leukemic cells via the mitochondrial pathway and has the potential to eradica ...
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Patient Derived Tumor Xenografts
Patient derived xenografts (PDX) are models of cancer where the tissue or cells from a patient's tumor are implanted into an immunodeficient or humanized mouse. PDX models are used to create an environment that allows for the natural growth of cancer, its monitoring, and corresponding treatment evaluations for the original patient. Methods of tumor xenotransplantation Several types of immunodeficient mice can be used to establish PDX models: athymic nude mice, severely compromised immune deficient (SCID) mice, NOD-SCID mice, and recombination-activating gene 2 (Rag2)-knockout mice. The mice used must be immunocompromised to prevent transplant rejection. The NOD-SCID mouse is considered more immunodeficient than the nude mouse, and therefore is more commonly used for PDX models because the NOD-SCID mouse does not produce natural killer cells. When human tumors are resected, necrotic tissues are removed and the tumor can be mechanically sectioned into smaller fragments, chemically ...
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Monastrol
Monastrol is a cell-permeable small molecule inhibitor discovered by Thomas U. Mayer in the lab of Tim Mitchison. Monastrol was shown to inhibit the kinesin A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzy ...-5 (also known as KIF11, Kinesin Eg5), a motor protein important for spindle bipolarity. Mechanism of action Monastrol binds to a long loop that is specific to the Eg5 (also known as KIF11 or kinesin-5) kinesin family, and allosterically inhibits ATPase activity of the kinesin References GABAA receptor positive allosteric modulators GHB receptor agonists Thioureas Pyrimidines {{pharma-stub ...
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Processivity
In molecular biology and biochemistry, processivity is an enzyme's ability to catalyze "consecutive reactions without releasing its substrate". For example, processivity is the average number of nucleotides added by a polymerase enzyme, such as DNA polymerase, per association event with the template strand. Because the binding of the polymerase to the template is the rate-limiting step in DNA synthesis, the overall rate of DNA replication during S phase of the cell cycle is dependent on the processivity of the DNA polymerases performing the replication. DNA clamp proteins are integral components of the DNA replication machinery and serve to increase the processivity of their associated polymerases. Some polymerases add over 50,000 nucleotides to a growing DNA strand before dissociating from the template strand, giving a replication rate of up to 1,000 nucleotides per second. DNA binding interactions Polymerases interact with the phosphate backbone and the minor groove of the DNA ...
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Fluorophore
A fluorophore (or fluorochrome, similarly to a chromophore) is a fluorescent chemical compound that can re-emit light upon light excitation. Fluorophores typically contain several combined aromatic groups, or planar or cyclic molecules with several π bonds. Fluorophores are sometimes used alone, as a tracer in fluids, as a dye for staining of certain structures, as a substrate of enzymes, or as a probe or indicator (when its fluorescence is affected by environmental aspects such as polarity or ions). More generally they are covalently bonded to a macromolecule, serving as a marker (or dye, or tag, or reporter) for affine or bioactive reagents (antibodies, peptides, nucleic acids). Fluorophores are notably used to stain tissues, cells, or materials in a variety of analytical methods, i.e., fluorescent imaging and spectroscopy. Fluorescein, via its amine-reactive isothiocyanate derivative fluorescein isothiocyanate (FITC), has been one of the most popular fluorophores. Fro ...
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