Cdr2 | |
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Identifiers | |
Organism | |
Symbol | SPAC57A10.02 |
Entrez | 2541590 |
Cdr2 is a serine/threonine protein kinase mitotic regulator in the fission yeast S. pombe. It is encoded by the P87050 2247 bp ORF on the cosmid 57A10. [1] The protein is 775 amino acids in length. Cdr2 is a member of the GIN4 family of kinases, which prevent progression of mitosis if there is a problem with septin. The N-terminus contains a sequence characteristic of serine/threonine protein kinase activity. The C-terminus, while non-catalytic, is necessary for proper localization of Cdr2 during interphase.
Cdr2 null constructs behave similarly to wild-type constructs; the only difference being a slight delay into mitosis and consequently, cells are slightly larger than in wild-type constructs. Therefore, Cdr2 is non-essential. [1] Cdr2 regulates mitotic entry through direct inhibition of Wee1, which is then unable to continue to Cdk1 and subsequently start mitosis.
During interphase (G1, S, G2), Cdr2 is localized in a wide medial band that is centered on the nucleus. The C-terminus is required for correct localization; cleavage of any number of residues close to the carboxy terminus results in abnormal distribution. [2] Pom1 phosphorylates Cdr2 on the C-terminus, and prevents it from spreading beyond the medial band. The width of the cortical band increases proportionately with the length of the growing cell; the final limit is at approximately 30% of the total cell length before the cell enters mitosis. [2] When the cell enters mitosis, Cdr2 is distributed diffusely through the cytoplasm; there is no detectable cortical band in metaphase in anaphase. During septation at the end of anaphase, Cdr2 localizes to the contractile ring. After cytokinesis, Cdr2 is again distributed in a broad medial band centered on the nucleus. [1]
Pom1 is a serine/threonine protein kinase that localizes to the cell tips. It is a partial mechanism for the formation of the medial distribution of Cdr2 in the cell; Pom1 has been demonstrated to prevent Cdr2 from diffusing into the non-growing end of the cell in interphase. [3] As seen in figure 1, Pom1 directly inhibits Cdr2. This is done through phosphorylation of Cdr2 on a residue between 423 and 532 on the non-catalytic C-terminus. Once phosphorylated, Cdr2 is unable to inhibit the kinase Wee1, which is then able to maintain CDK1 in a hyper-phosphorylated state incapable of progression into mitosis. Mutation and deletion of Cdr2 result in a delay into mitotic entry, leading to larger cells. However, the cells still enter mitosis, presumably because Cdr2 is the link in only one pathway that couples cell length to mitotic entry. Thus, Cdr2 is non-essential to the decision to enter mitosis.
Pom1 is distributed in a gradient from the cell tips, with the maximum concentration in the cell tips and the lower concentrations in the medial region of the cell, roughly overlapping with the wide medial band occupied by Cdr2. In small cells, there is a higher level of overlap between Pom1 and Cdr2, leading to a greater degree of inhibition of Cdr2; conversely Cdr2 is unable to inhibit Wee1, which is then free to inhibit CDK1. Therefore, Cdr2 functions as part of a cell-size sensor pathway. In larger cells, there is much lower degree of overlap between Pom1 and Cdr2, allowing Cdr2 to inhibit Wee1; CDK1 is then able to promote mitotic entry.
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that causes it to divide into two daughter cells. These events include the duplication of its DNA and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division.
Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there are two distinct types of cell division: a vegetative division (mitosis), producing daughter cells genetically identical to the parent cell, and a cell division that produces haploid gametes for sexual reproduction (meiosis), reducing the number of chromosomes from two of each type in the diploid parent cell to one of each type in the daughter cells. In cell biology, mitosis (/maɪˈtoʊsɪs/) 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 animal cell cycle—the division of the mother cell into two genetically identical daughter cells. Meiosis undergoes two divisions resulting in four haploid daughter cells. Homologous chromosomes are separated in the first division of meiosis, such that each daughter cell has one copy of each chromosome. These chromosomes have already been replicated and have two sister chromatids which are then separated during the second division of meiosis. Both of these cell division cycles are used in the process of sexual reproduction at some point in their life cycle. Both are believed to be present in the last eukaryotic common ancestor.
Schizosaccharomyces pombe, also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measure 3 to 4 micrometres in diameter and 7 to 14 micrometres in length. Its genome, which is approximately 14.1 million base pairs, is estimated to contain 4,970 protein-coding genes and at least 450 non-coding RNAs.
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.
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis is greater than the overall rate of cellular degradation.
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.
G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the onset of prophase, the first phase of mitosis in which the cell’s chromatin condenses into chromosomes.
Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, with progression through the various phases of the cell cycle occurring only when favorable conditions are met. There are many checkpoints in the cell cycle, but the three major ones are: the G1 checkpoint, also known as the Start or restriction checkpoint or Major Checkpoint; the G2/M checkpoint; and the metaphase-to-anaphase transition, also known as the spindle checkpoint. Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein subunits called cyclins, different forms of which are produced at each stage of the cell cycle to control the specific events that occur therein.
The G1/S transition is a stage in the cell cycle at the boundary between the G1 phase, in which the cell grows, and the S phase, during which DNA is replicated. It is governed by cell cycle checkpoints to ensure cell cycle integrity and the subsequent S phase can pause in response to improperly or partially replicated DNA. During this transition the cell makes decisions to become quiescent, differentiate, make DNA repairs, or proliferate based on environmental cues and molecular signaling inputs. The G1/S transition occurs late in G1 and the absence or improper application of this highly regulated checkpoint can lead to cellular transformation and disease states such as cancer
Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in the budding yeast S. cerevisiae, and the fission yeast S. pombe, where it is encoded by genes cdc28 and cdc2, respectively. With its cyclin partners, Cdk1 forms complexes that phosphorylate a variety of target substrates ; phosphorylation of these proteins leads to cell cycle progression.
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 the fly Drosophila melanogaster (Polo), budding yeast (Cdc5) and fission yeast (Plo1). Vertebrates and other animals, 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.
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 gene.
Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase also known as Myt1 kinase is an enzyme that in humans is encoded by the PKMYT1 gene.
MASTL is an official symbol provided by HGNC for human gene whose official name is micro tubule associated serine/threonine kinase like. This gene is 32,1 kbps long. This gene is also known as GW, GWL, THC2, MAST-L, GREATWALL. This is present in mainly mammalian cells like human, house mouse, cattle, monkey, etc. It is in the 10th chromosome of the mammalian nucleus. Recent studies have been carried on zebrafish and frogs. This gene encodes for the protein micro tubule associated serine/threonine kinase and its sub-classes.
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe. Wee1 has a molecular mass of 96 kDa and is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdk1. Wee1 has homologues in many other organisms, including mammals.
Pom1 is a polarity protein kinase in fission yeast, Schizosaccharomyces pombe, that localizes to cell ends and regulates cell division. As the cell lengthens, the level of Pom1 in the middle declines, which triggers mitosis.
A series of biochemical switches control transitions between and within the various phases of the cell cycle. The cell cycle is a series of complex, ordered, sequential events that control how a single cell divides into two cells, and involves several different phases. The phases include the G1 and G2 phases, DNA replication or S phase, and the actual process of cell division, mitosis or M phase. During the M phase, the chromosomes separate and cytokinesis occurs.
Cdc14 and Cdc14 are a gene and its protein product respectively. Cdc14 is found in most of the eukaryotes. Cdc14 was defined by Hartwell in his famous screen for loci that control the cell cycle of Saccharomyces cerevisiae. Cdc14 was later shown to encode a protein phosphatase. Cdc14 is dual-specificity, which means it has serine/threonine and tyrosine-directed activity. A preference for serines next to proline is reported. Many early studies, especially in the budding yeast Saccharomyces cerevisiae, demonstrated that the protein plays a key role in regulating late mitotic processes. However, more recent work in a range of systems suggests that its cellular function is more complex.
The G2-M DNA damage checkpoint is an important cell cycle checkpoint in eukaryotic organisms that ensures that cells don't initiate mitosis until damaged or incompletely replicated DNA is sufficiently repaired. Cells with a defective G2-M checkpoint will undergo apoptosis or death after cell division if they enter the M phase before repairing their DNA. The defining biochemical feature of this checkpoint is the activation of M-phase cyclin-CDK complexes, which phosphorylate proteins that promote spindle assembly and bring the cell to metaphase.