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BUB1
Mitotic checkpoint serine/threonine-protein kinase BUB1 also known as BUB1 (budding uninhibited by benzimidazoles 1) is an enzyme that in humans is encoded by the ''BUB1'' gene. Bub1 is a serine/threonine protein kinase first identified in genetic screens of ''Saccharomyces cerevisiae''. The protein is bound to kinetochores and plays a key role in the establishment of the mitotic spindle checkpoint and chromosome congression. The mitotic checkpoint kinase is evolutionarily conserved in organisms as diverse as ''Saccharomyces cerevisiae'' and humans. Loss-of-function mutations or absence of Bub1 has been reported to result in aneuploidy, chromosomal instability ( CIN) and premature senescence. Structure Bub1p comprises a conserved N-terminal region, a central non-conserved region and a C-terminal serine/threonine kinase domain. The N-terminal region mediates binding of Hs-BUB1 to the mitotic kinetochore protein blinkin (a protein also commonly referred to as AF15q14). The latte ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BUB1B
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. Function This gene encodes a kinase involved in spindle checkpoint function and chromosome segregation. The protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/ cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. Impaired spindle checkpoint function has been found in many forms of cancer. Increased expression of BubR1 in mice extends a healthy lifespan. * Clinical Significance Bub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BUB3
Mitotic checkpoint protein BUB3 is a protein that in humans is encoded by the ''BUB3'' gene. Bub3 is a protein involved with the regulation of the Spindle checkpoint, Spindle Assembly Checkpoint (SAC); though BUB3 is non-essential in yeast, it is essential in higher eukaryotes. As one of the checkpoint proteins, Bub3 delays the irreversible onset of anaphase through direction of kinetochore localization during prometaphase to achieve biorientation. In directing the kinetochore-microtubule interaction, this ensures the proper (and consequently, bioriented) attachment of the chromosomes prior to anaphase. Bub3 and its related proteins that form the Spindle Assembly Checkpoint (SAC) inhibit the action of the Anaphase-promoting complex, Anaphase Promoting Complex (APC), preventing early anaphase entry and mitotic exit; this serves as a mechanism for the fidelity of chromosomal segregation. Function Bub3 is a crucial component in the formation of the mitotic spindle assembly complex ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Spindle Checkpoint
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 (bipolar orientation). 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. Overview and importance The beginning of metaphase is characterized by the connection of the microtubules to the kinetochores of the chrom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Kinetochore
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. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term ''kinetochore'' (= movement place) has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932. Monocentric organisms, including vertebrates, fungi, and most plants, have a single centromeric region on each chromosome which assembles a single, localized kinetochore. Holocentric organisms, such as nematodes and some plants, assemble a kinetochore along the entire length of a chromosome. Ki ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAD2
Mad2 (mitotic arrest deficient 2) 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 (MAD2L1 and MAD2L2) 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. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SGOL1
Shugoshin 1 or Shugoshin-like 1, is a protein that in humans is encoded by the ''SGO1'' gene. Model organisms Model organisms have been used in the study of SGOL1 function. A conditional knockout mouse line, called ''Sgol1tm1a(EUCOMM)Wtsi'' has been generated. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty six tests were carried out on mutant mice and three significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and thus none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and a decreased regulatory T cell number was observed in male animals. Mechanisms A physical mechanism that guarantees the accurate segregation of sister chromatids during mitosis arises from the ring shaped cohesin complex consisting of 4 subunits (SMC1A/ B, SMC3, SCC1, and SA1/ 2 in humans). This complex encircles the two sister chromatids and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CDC20
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. CDC20 appears to act as a regulatory protein interacting with many other proteins at multiple points in the cell cycle. It is required for two microtubule-dependent processes: nuclear movement prior to an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mad1
Mad1 is a non-essential protein which in yeast has a function in the spindle assembly checkpoint (SAC). This checkpoint monitors chromosome attachment to spindle microtubules and prevents cells from starting anaphase until the spindle is built up. The name Mad refers to the observation that mutant cells are mitotic arrest deficient (MAD) during microtubule depolymerization. Mad1 recruits the anaphase inhibitor Mad2 to unattached kinetochores and is essential for Mad2-Cdc20 complex formation ''in vivo'' but not ''in vitro''. ''In vivo'', Mad1 acts as a competitive inhibitor of the Mad2-Cdc20 complex. Mad1 is phosphorylated by Mps1 which then leads together with other activities to the formation of the mitotic checkpoint complex (MCC). Thereby it inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C). Homologues of Mad1 are conserved in eukaryotes from yeast to mammals. Introduction In the early 90s, yeast genes were identified which mutations resulted in a de ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction ra ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prophase
Prophase () is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin reticulum and the disappearance of the nucleolus. Staining and microscopy Microscopy can be used to visualize condensed chromosomes as they move through meiosis and mitosis. Various DNA stains are used to treat cells such that condensing chromosomes can be visualized as the move through prophase. The giemsa G-banding technique is commonly used to identify mammalian chromosomes, but utilizing the technology on plant cells was originally difficult due to the high degree of chromosome compaction in plant cells. G-banding was fully realized for plant chromosomes in 1990. During both meiotic and mitotic prophase, giemsa staining can be applied to cells to elicit G-banding in chromosomes. Silver staining, a more modern technology, in conjunction ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PLK1
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'' (polo-like kinase 1) gene. Structure PLK1 consists of 603 amino acids and is 66kDa. In addition to the N-terminus kinase domain, there are two conserved polo-box regions of 30 amino acids at the C-terminus. Kinase activity is regulated at least in part, by the polo-boxes that are functionally important for both auto-inhibition and subcellular localization. Localization During interphase, PLK1 localizes to centrosomes. In early mitosis, it associates with mitotic spindle poles. A recombinant GFP-PLK1 protein localizes to centromere/kinetochore region, suggesting a possible role for chromosome separation. Cell cycle regulation Plk1 is an early trigger for G2/M transition. Plk1 supports the functional maturation of the centrosome in late G2/early prophase and establishment of the bipolar spindl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Anaphase-promoting Complex
Anaphase-promoting complex (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11–13 subunit proteins, including a cullin (Apc2) and RING (Apc11) subunit much like SCF. Other parts of the APC/C have unknown functions but are highly conserved. It was the discovery of the APC/C (and SCF) and their key role in eukaryotic cell-cycle regulation that established the importance of ubiquitin-mediated proteolysis in cell biology. Once perceived as a system exclusively involved in removing damaged protein from the cell, ubiquitination and subsequent protein degradation by the proteasome is now perceived as a universal regulatory mechanism for signal transduction whose importance approaches that of protein phosphorylation. In 2014, the APC/C was mapped in 3D at a resolution of less than a nanometre, which also uncovered its secondary structure. This finding ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
