Maturation-promoting factor (abbreviated MPF, also called mitosis-promoting factor or M-Phase-promoting factor) is the cyclin-Cdk complex that was discovered first in frog eggs. It stimulates the mitotic and meiotic phases of the cell cycle. MPF promotes the entrance into mitosis (the M phase) from the G2 phase by phosphorylating multiple proteins needed during mitosis. MPF is activated at the end of G2 by a phosphatase, which removes an inhibitory phosphate group added earlier.
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Seciclib causes egg activation by inhibiting protein kinases which results in the inactivation of the maturation promoting factor (MPF).
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The S-phase-promoting factor (SPF) is a CDK-cyclin complex that induces the S-phase (synthesis phase) of the cell cycle. The S-phase-promoting factor (SPF) is inhibited by Sic1 (a protein which also is a stoichiometric inhibitor of Cdk1-Clb and B-type cyclins). Sic1 releases SPF from inhibition after it is phosphorylated by G1-cyclin-CDK. The phosphorylation marking SPF for polyubiquitination by the SCF ubiquitin ligase.
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Cyclin B is a member of the cyclin family. Cyclin B is a mitotic cyclin. The amount of cyclin B (which binds to Cdk1) and the activity of the cyclin B-Cdk complex rise through the cell cycle until mitosis, where they fall abruptly due to degradation of cyclin B (Cdk1 is constitutively present). The complex of Cdk and cyclin B is called maturation promoting factor or mitosis promoting factor (MPF).
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Meiotic arrest occurs mainly due to increased cAMP levels in the oocyte, which regulates key regulator cyclin kinase complex maturation promoting factor (MPF). cGMPs produced by somatic follicular cells further regulate cAMP concentration in the oocyte.
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Pleiotrophin was initially recognized as a neurite outgrowth-promoting factor present in rat brain around birth and as a mitogen toward fibroblasts isolated from bovine uterus tissue. Together with midkine these growth-factors constitute a family of (developmentally regulated) secreted heparin-binding proteins now known as the neurite growth- promoting factor (NEGF) family. During embryonic and early postnatal development, pleiotrophin is expressed in the central and peripheral nervous system and also in several non-neural tissues, notably lung, kidney, gut and bone. Pleiotrophin is also expressed by several tumor cells and is thought to be involved in tumor angiogenesis.
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Cyclin A2 is involved in the G2/M transition but it cannot independently form a maturation promoting factor (MPF). Recent studies have shown that the cyclin A2-CDK1 complex triggers cyclin B1-CDK1 activation which results in chromatin condensation and the breakdown of the nuclear envelope.
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During mitosis, lamins are phosphorylated by Mitosis-Promoting Factor (MPF), which drives the disassembly of the lamina and the nuclear envelope. This allows chromatin to condense and the DNA to be replicated. After chromosome segregation, dephosphorylation of nuclear lamins by a phosphatase promotes reassembly of the nuclear envelope.
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The mitosis promoting factor MPF also regulates DNA-damage induced apoptosis. Negative regulation of MPF by WEE1 causes aberrant mitosis and thus resistance to DNA-damage induced apoptosis. Kruppel-like factor 2 (KLF2) negatively regulates human WEE1, thus increasing sensitivity to DNA-damage induced apoptosis in cancer cells.
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The rapid cell cycles are facilitated by maintaining high levels of proteins that control cell cycle progression such as the cyclins and their associated cyclin- dependent kinases (cdk). The complex Cyclin B/CDK1 a.k.a. MPF (maturation promoting factor) promotes entry into mitosis. The processes of karyokinesis (mitosis) and cytokinesis work together to result in cleavage.
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Complex formation results in activation of the Cdk active site. Cyclins themselves have no enzymatic activity but have binding sites for some substrates and target the Cdks to specific subcellular locations. Cyclins, when bound with the dependent kinases, such as the p34/cdc2/cdk1 protein, form the maturation-promoting factor. MPFs activate other proteins through phosphorylation.
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Cyclin B1 is a regulatory protein involved in mitosis. The gene product complexes with p34 (Cdk1) to form the maturation- promoting factor (MPF). Two alternative transcripts have been found, a constitutively expressed transcript and a cell cycle-regulated transcript that is expressed predominantly during G2/M phase of the cell cycle. The different transcripts result from the use of alternate transcription initiation sites.
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The first few nucleotides added by PAP are added very slowly, but the short polyadenine tail is then bound by PABPII, which accelerates the rate of adenine addition by PAP. The final tail is about 200-250 adenine nucleotides long. PAP is phosphorylated by mitosis-promoting factor, a key regulator of the cell cycle. High phosphorylation levels decrease PAP activity.
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The gene is located on the second human chromosome, near the end of the chromosome's arm (2q35), between the codons 85-87 and 1387-1389. It contains 6042 bp and 11 exons When transcribed, it gives a 1859 bp mRNA. . The vascular endothelial growth factor is a promoting factor of the protein synthesis and localisation in the different parts of the cells. The protein's expression is higher in the intracellular than in the extracellular space.
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In S. pombe, Wee1 is phosphorylated Cdk1 and cyclin B make up the maturation promoting factor (MPF) which promotes the entry into mitosis. It is inactivated by phosphorylation through Wee1 and activated by the phosphatase Cdc25C. Cdc25C in turn is activated by Polo kinase and inactivated by Chk1. Thus in S. pombe Wee1 regulation is mainly under the control of phosphorylation through the polarity kinase, Pom1's, pathway including Cdr2 and Cdr1.
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Leukocyte-promoting factor, more commonly known as leukopoietin, is a category of substances produced by neutrophils when they encounter a foreign antigen. Leukopoietin stimulates the bone marrow to increase the rate of leukopoiesis in order to replace the neutrophils that will inevitably be lost when they begin to phagocytose the foreign antigens. Leukocyte-promoting factors include colony stimulating factors (CSFs) (produced by monocytes and T lymphocytes), interleukins (produced by monocytes, macrophages, and endothelial cells), prostaglandins, and lactoferrin.
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Certain intracellular pathogens such as the bacterial species Listeria monocytogenes and Shigella flexneri can manipulate host cell actin polymerization to move through the cytosol and spread to neighboring cells (see below). Studies of these bacteria, especially of Listeria Actin assembly-inducing protein (ActA), have resulted in further understanding of the actions of WASP. ActA is a nucleation promoting factor that mimics WASP. It is expressed polarized to the posterior end of the bacterium, allowing Arp2/3-mediated actin nucleation.
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Pleiotrophin (PTN) also known as heparin-binding brain mitogen (HBBM) or heparin-binding growth factor 8 (HBGF-8) or neurite growth-promoting factor 1 (NEGF1) or heparin affinity regulatory peptide (HARP) or heparin binding growth associated molecule (HB-GAM) is a protein that in humans is encoded by the PTN gene. Pleiotrophin is an 18-kDa growth factor that has a high affinity for heparin. It is structurally related to midkine and retinoic acid induced heparin-binding protein.
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Midkine (MK or MDK), also known as neurite growth-promoting factor 2 (NEGF2), is a protein that in humans is encoded by the MDK gene. Midkine is a basic heparin-binding growth factor of low molecular weight, and forms a family with pleiotrophin (NEGF1, 46% homologous with MK). It is a nonglycosylated protein, composed of two domains held by disulfide bridges. It is a developmentally important retinoic acid-responsive gene product strongly induced during mid- gestation, hence the name midkine.
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In anatomy, a crystallin is a water-soluble structural protein found in the lens and the cornea of the eye accounting for the transparency of the structure. It has also been identified in other places such as the heart, and in aggressive breast cancer tumors. Since it has been shown that lens injury may promote nerve regeneration, crystallin has been an area of neural research. So far, it has been demonstrated that crystallin β b2 (crybb2) may be a neurite-promoting factor.
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Though Wee1 is a fairly conserved negative regulator of mitotic entry, no general mechanism of cell size control in G2 has yet been elucidated. Biochemically, the end of G2 phase occurs when a threshold level of active cyclin B1/CDK1 complex, also known as Maturation promoting factor (MPF) has been reached. The activity of this complex is tightly regulated during G2. In particular, the G2 checkpoint arrests cells in G2 in response to DNA damage through inhibitory regulation of CDK1.
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Elevated concentrations of intra-oocyte cAMP regulates meiotic arrest and prevents meiotic resumption. Intracellular cAMP constantly activates PKA, which then activates nuclear kinase Weel/MtyI. Weel/Mtyl inhibits cell division cycle 25B (CDC25B) which is a main activator for Cyclin-dependent kinase (CDK). This leads to the inactivation of maturation promoting factor (MPF) as MPF comprises of CDK and Cyclin B. MPF is an essential regulator for M-phase transition and plays a key role in meiotic resumption in oocytes and its post-GVBD activities.
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PCC was first reported in 1968, of viral-infected cells showing strange appearance of chromosomes. It was found that the strange appearance was selectively observed in S-phase nuclei, and therefore concluded that the nuclei of cells fused in mitotic cells condensed prematurely by unknown material which accumulated in mitotic cells, and observed chromosome structures that are equivalent to those in cell fusion. This material was named as the mitosis promoting factor (MPF). The precise mechanism of chromosome condensation, as well as the premature condensation, is still in question.
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The protein product of WAS is known as WASp. It contains 502 amino acids and is mainly expressed in hematopoietic cells (the cells in the bone marrow that develop into blood cells). The main function of WASp is to activate actin polymerization by serving as a nucleation-promoting factor (NPF) for the Arp2/3 complex, which generates branched actin filaments. Several proteins can serve as NPFs, and it has been observed that in WAS platelets the Arp2/3 complex functions normally, indicating that WASp is not required for its activation in platelets.
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Cell cycle progression is controlled by ordered action of cyclin-dependent kinases (CDKs), activated by specific cyclins that demarcate phases of the cell cycle. Mitotic cyclins, which persist in the cell for only a few minutes, have one of the shortest life spans of all intracellular proteins. After a CDK-cyclin complex has performed its function, the associated cyclin is polyubiquitinated and destroyed by the proteasome, which provides directionality for the cell cycle. In particular, exit from mitosis requires the proteasome-dependent dissociation of the regulatory component cyclin B from the mitosis promoting factor complex.
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Macrophages also play a role in inducing the proliferation of Schwann cells that occurs during Wallerian degeneration. Supernatant has been collected from medium in which macrophages are active in myelin phagocytosis where lysosomal processing of the myelin occurs within the macrophage. The supernatant contains a mitogenic factor, a mitosis promoting factor, that is characterized heat and trypsin sensitivity, both of which characterize it as a peptide. Treatment of Schwann cells with the collected supernatant shows that it is a mitogenic factor and thus plays an important role in the proliferation of Schwann cells.
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Mitotic entry is determined by a threshold level of active cyclin-B1/CDK1 complex, also known as cyclin-B1/Cdc2 or the maturation promoting factor (MPF). Active cyclin-B1/CDK1 triggers irreversible actions in early mitosis, including centrosome separation, nuclear envelope breakdown, and spindle assembly. In vertebrates, there are five cyclin B isoforms (B1, B2, B3, B4, and B5), but the specific role of each of these isoforms in regulating mitotic entry is still unclear. It is known that cyclin B1 can compensate for loss of both cyclin B2 (and vice versa in Drosophila).
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Fig. 1 Actin assembly induced by bacterial protein ActA (shown in green). Mammalian proteins involved in this process are: Profilin (P), Vasodilator-stimulated phosphoprotein (VASP) and actin-related-protein 2 and 3 complex (Arp2/3 complex) as well as actin. ActA is a protein which acts as a mimic of Wiskott- Aldrich syndrome protein (WASP), a nucleation promoting factor (NPF) present in host cells. NPFs in the mammalian cell recruit and bind to the already existing actin-related-protein 2 and 3 complex (Arp2/3 complex) and induce an activating conformational change of the Arp2/3 complex.
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Medical inventions developed at Toronto include the glycaemic index, the infant cereal Pablum, the use of protective hypothermia in open heart surgery and the first artificial cardiac pacemaker. The first successful single-lung transplant was performed at Toronto in 1981, followed by the first nerve transplant in 1988, and the first double-lung transplant in 1989. Researchers identified the maturation promoting factor that regulates cell division, and discovered the T-cell receptor, which triggers responses of the immune system. The university is credited with isolating the genes that cause Fanconi anemia, cystic fibrosis and early-onset Alzheimer's disease, among numerous other diseases.
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During G2 phase of the cell cycle, Cdk1 and cyclin B1 makes a complex and forms maturation promoting factor (MPF). The complex accumulates in the nucleus due to phosphorylation of the cyclin B1 at multiple sites, which inhibits nuclear export of the complex. Phosphorylation of Thr19 and Tyr15 residues of Cdk1 by Wee1 and MYT1 keeps the complex inactive and inhibits entry into mitosis whereas dephosphorylation of Cdk1 by CDC25C phosphatase at Thr19 and Tyr15 residues, activates the complex which is necessary in order to enter mitosis. Cdc25C phosphatase is present in the cytoplasm and in late G2 phase it is translocated into the nucleus by signaling such as PIK1, PIK3.
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In 1971, two independent teams of researchers (Yoshio Masui and Clement Markert, as well as Dennis Smith and Robert Ecker) found that frog oocytes arrested in G2 could be induced to enter M phase by microinjection of cytoplasm from oocytes that had been hormonally stimulated with progesterone. Because the entry of oocytes into meiosis is frequently referred to as oocyte maturation, this cytoplasmic factor was called maturation promoting factor (MPF). Further studies showed, however, that the activity of MPF is not restricted to the entry of oocytes into meiosis. To the contrary, MPF is also present in somatic cells, where it induces entry into M phase of the mitotic cycle.
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The toxin, known as pertussis toxin (or PTx), inhibits G protein coupling that regulates an adenylate cyclase-mediated conversion of ATP to cyclic AMP. The end result is that phagocytes convert too much ATP to cAMP, causing disturbances in cellular signaling mechanisms, and preventing phagocytes from correctly responding to the infection. PTx, formerly known as lymphocytosis- promoting factor, causes a decrease in the entry of lymphocytes into lymph nodes, which can lead to a condition known as lymphocytosis, with a complete lymphocyte count of over 4000/μl in adults or over 8000/μl in children. Beside targeting lymphocytes, it limits neutrophil migration to the lungs.
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In 1932 an outbreak of whooping cough hit Atlanta, Georgia, prompting pediatrician Leila Denmark to begin her study of the disease. Over the next six years her work was published in the Journal of the American Medical Association, and in partnership with Emory University and Eli Lilly & Company, she developed the first pertussis vaccine. In 1942 American scientists Grace Eldering, Loney Gordon, and Pearl Kendrick combined the whole-cell pertussis vaccine with diphtheria and tetanus toxoids to generate the first DTP combination vaccine. To minimize the frequent side effects caused by the pertussis component, Japanese scientist Yuji Sato developed an acellular vaccine consisting of purified haemagglutinins (HAs: filamentous strep throat and leukocytosis-promoting-factor HA), which are secreted by B. pertussis.
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G2 is commenced by E2F-mediated transcription of cyclin A, which forms the cyclin A-Cdk2 complex. In order to proceed into mitosis, the cyclin B-Cdk1 complex (first discovered as MPF or M-phase promoting factor; Cdk1 is also known as Cdc2 in fission yeast and Cdc28 in budding yeast) is activated by Cdc25, a protein phosphatase. As mitosis starts, the nuclear envelope disintegrates, chromosomes condense and become visible, and the cell prepares for division. Cyclin B-Cdk1 activation results in nuclear envelope breakdown, which is a characteristic of the initiation of mitosis. The cyclin B-Cdk1 complex participates in a regulatory circuit in which Cdk1 can phosphorylate and activate its activator, Cdc25 (positive feedback), and phosphorylate and inactivate its inactivator, the kinase Wee1 (double-negative feedback).
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As with most processes in the body, the cell cycle is highly regulated to prevent the synthesis of mutated cells and uncontrolled cell division that leads to tumor formation. The cell cycle control system is biochemically based so that the proteins of the mitosis promoting factor (MPF) control the transition from one phase to the next based on a series of checkpoints. MPF is a protein dimer made up of cyclin and cyclin-dependent kinase (Cdk), a serine and threonine kinase, which come together at different points in the cycle to control cell progression through the cycle. When cyclin binds to Cdk, Cdk becomes activated and phosphorylates serine and threonine on other proteins causing the activation and degradation of other proteins allowing the cell to transition through the cell cycle.
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By 1927 a series of experiments, performed in part by Elmer McCollum and others, had shown that water-soluble vitamin B was primarily made of two parts: the anti-neuritic factor B1 (now known as thiamine) and the more heat-stable factor B2. By 1932 Gyorgy had found that the heat-stable B2 was not in fact a single substance, but actually a complex made up of two factors: the growth-promoting factor (later found to be riboflavin) and the anti-pellagra factor (later found to be vitamin B6). Gyorgy, in collaboration with chemist Richard Kuhn and physician Th. Wagner- Jauregg at the University of Heidelberg, had noticed that rats kept on a B2-free diet were unable to gain weight. Isolation of concentrated B2 from yeast revealed the presence of a bright yellow-green fluorescent product that when fed to the rat, restored normal growth.
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Dr. Chiorazzi's research interests revolve around understanding the activation and maturation of B-lymphocytes in health and disease, in particular chronic lymphocytic leukemia (CLL). Dr. Chiorazzi and his colleagues have demonstrated that: CLL cells are responsive to signals from the internal microenvironment, in particular those delivered by the B-cell antigen receptor (BCR) leading to leukemic cell proliferation and maturation or death; BCR-induced signals are likely delivered by common self antigens and are mediated through sets of BCRs of remarkably similar amino acid structure; patients with CLL segregate into two subgroups based on BCR structure that differ dramatically in clinical outcome; CLL cells proliferate and die in vivo at rates higher than originally appreciated. These findings have led to the view that (auto)antigen drive is a promoting factor in the development and evolution of CLL and have been pivotal in refining patient prognosis.
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Cryo-EM structure of the DNA-bound PolD–PCNA processive complex Structural basis for DNA binding by the PolD–PCNA complex A DNA clamp, also known as a sliding clamp or β-clamp, is a protein complex that serves as a processivity- promoting factor in DNA replication. As a critical component of the DNA polymerase III holoenzyme, the clamp protein binds DNA polymerase and prevents this enzyme from dissociating from the template DNA strand. The clamp- polymerase protein–protein interactions are stronger and more specific than the direct interactions between the polymerase and the template DNA strand; because one of the rate-limiting steps in the DNA synthesis reaction is the association of the polymerase with the DNA template, the presence of the sliding clamp dramatically increases the number of nucleotides that the polymerase can add to the growing strand per association event. The presence of the DNA clamp can increase the rate of DNA synthesis up to 1,000-fold compared with a nonprocessive polymerase.
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Several nanotechnology researchers state that the bulk of risk from nanotechnology comes from the potential to lead to war, arms races and destructive global government. Several reasons have been suggested why the availability of nanotech weaponry may with significant likelihood lead to unstable arms races (compared to e.g. nuclear arms races): (1) A large number of players may be tempted to enter the race since the threshold for doing so is low; (2) the ability to make weapons with molecular manufacturing will be cheap and easy to hide; (3) therefore lack of insight into the other parties' capabilities can tempt players to arm out of caution or to launch preemptive strikes; (4) molecular manufacturing may reduce dependency on international trade, a potential peace-promoting factor; (5) wars of aggression may pose a smaller economic threat to the aggressor since manufacturing is cheap and humans may not be needed on the battlefield. Since self-regulation by all state and non-state actors seems hard to achieve, measures to mitigate war- related risks have mainly been proposed in the area of international cooperation.
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Several reasons have been suggested why the availability of nanotech weaponry may with significant likelihood lead to unstable arms races (compared to e.g. nuclear arms races): (1) A large number of players may be tempted to enter the race since the threshold for doing so is low; (2) the ability to make weapons with molecular manufacturing might be cheap and easy to hide; (3) therefore lack of insight into the other parties' capabilities can tempt players to arm out of caution or to launch preemptive strikes; (4) molecular manufacturing may reduce dependency on international trade, a potential peace-promoting factor; (5) wars of aggression may pose a smaller economic threat to the aggressor since manufacturing is cheap and humans may not be needed on the battlefield. Self-regulation by all state and non-state actors has been called hard to achieve, so measures to mitigate war-related risks have mainly been proposed in the area of international cooperation. International infrastructure may be expanded giving more sovereignty to the international level.
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