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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] |
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] |
MAD2L1
Mitotic spindle assembly checkpoint protein MAD2A is a protein that in humans is encoded by the ''MAD2L1'' gene. Function MAD2L1 is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. MAD2L1 is related to the MAD2L2 gene located on chromosome 1. A MAD2 pseudogene has been mapped to chromosome 14. Interactions MAD2L1 has been shown to interact with: * ADAM17, * BUB1B, * CDC20, * CDC27 and * Estrogen receptor beta, * MAD2L2, * 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 ..., and * UBD. References Further reading * * * * * * * * * * * * * * * * * * {{PDB Gallery, geneid=4085 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
WD40 Repeat
The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold together to form a type of circular solenoid protein domain called the WD40 domain. Structure WD40 domain-containing proteins have 4 to 16 repeating units, all of which are thought to form a circularised beta-propeller structure (see figure to the right). The WD40 domain is composed of several repeats, a variable region of around 20 residues at the beginning followed by a more common repeated set of residues. These repeats typically form a four stranded anti-parallel beta sheet or blade. These blades come together to form a propeller with the most common being a 7 bladed beta propeller. The blades interlock so that the last beta strand of one repeat forms with the first three of the next repeat to form the 3D blade structure. Function WD40-repe ... [...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] |
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] |
Histone Deacetylase 2
Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the ''HDAC2'' gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones (H2A, H2B, H3, and H4). As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy. Though the functional role of the class to which HDAC2 belongs has been carefully studied, the mechanism by which HDAC2 interacts with histone deacetylases of other classes has yet to be elucidated. HDAC2 is broadly regulated by protein kinase 2 (CK2) and protein phosphatase 1 (PP1), but biochemical analysis suggests its regulation is more complex (evinced by the coexistence of HDAC1 and HDAC2 in three distinct protein complexes). Essentially, the mechanism by which HDAC2 is regulated is still unclear b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC1
Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the ''HDAC1'' gene. Function Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family and is a component of the histone deacetylase complex. It also interacts with retinoblastoma tumor-suppressor protein and this complex is a key element in the control of cell proliferation and differentiation. Together with metastasis-associated protein-2 MTA2, it deacetylates p53 and modulates its effect on cell growth and apoptosis. Model organisms Model organisms have been used in the study of HDAC1 function. A conditional knockout mouse line, called ''Hdac1tm1a(EUCOMM)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to inte ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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] |
RAE1
mRNA export factor is a protein that in humans is encoded by the ''RAE1'' gene. Mutations in the Schizosaccharomyces pombe Rae1 and Saccharomyces cerevisiae Gle2 genes have been shown to result in accumulation of poly(A)-containing mRNA in the nucleus, suggesting that the encoded proteins are involved in RNA export. The protein encoded by this gene is a homolog of yeast Rae1. It contains four WD40 motifs, and has been shown to localize to distinct foci in the nucleoplasm, to the nuclear rim, and to meshwork-like structures throughout the cytoplasm. This gene is thought to be involved in nucleocytoplasmic transport, and in directly or indirectly attaching cytoplasmic mRNPs to the cytoskeleton. Alternatively spliced transcript variants encoding the same protein have been found for this gene. Interactions RAE1 has been shown to interact with NUP98 Nuclear pore complex protein Nup98-Nup96 is a protein that in humans is encoded by the ''NUP98'' gene. Function Signal-mediated nucle ... [...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] |
Sister Chromatids
A sister chromatid refers to the identical copies (chromatids) formed by the DNA replication of a chromosome, with both copies joined together by a common centromere. In other words, a sister chromatid may also be said to be 'one-half' of the duplicated chromosome. A pair of sister chromatids is called a dyad. A full set of sister chromatids is created during the synthesis ( S) phase of interphase, when all the chromosomes in a cell are replicated. The two sister chromatids are separated from each other into two different cells during mitosis or during the second division of meiosis. Compare sister chromatids to homologous chromosomes, which are the two ''different'' copies of a chromosome that diploid organisms (like humans) inherit, one from each parent. Sister chromatids are by and large identical (since they carry the same alleles, also called variants or versions, of genes) because they derive from one original chromosome. An exception is towards the end of meiosis, after c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
