Pom1

Pom1
Identifiers
Organism	Schizosaccharomyces pombe
Symbol	SPAC2F7.03c
Entrez	2541889

Last updated May 02, 2019

Pom1 is a polarity protein kinase in fission yeast, Schizosaccharomyces pombe (S. 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.^[1]

In biochemistry, a kinase is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the substrate gains a phosphate group and the high-energy ATP molecule donates a phosphate group. This transesterification produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group. These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis. Kinases are part of the larger family of phosphotransferases. Kinases should not be confused with phosphorylases, which catalyze the addition of inorganic phosphate groups to an acceptor, nor with phosphatases, which remove phosphate groups. The phosphorylation state of a molecule, whether it be a protein, lipid, or carbohydrate, can affect its activity, reactivity, and its ability to bind other molecules. Therefore, kinases are critical in metabolism, cell signalling, protein regulation, cellular transport, secretory processes, and many other cellular pathways, which makes them very important to human physiology.

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.

The gene pom1 codes for a protein 1087 amino acids long with the protein kinase domain likely located at the carboxyl terminus.^[1] Pom1 regulates a signaling pathway that includes Cdk1 and ultimately regulates mitotic entry.^[2] Cells with mutant pom1 form a septa and growth zone, but show a host of abnormalities including misplaced or misoriented septa, bi-polar growth replaced with random growth at one end, or the mislocalization of the growth axis leading to abnormal branching.^[1]^[3]

In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions. Some genetic traits are instantly visible, such as eye color or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life.

In cell biology, mitosis is a part of the cell cycle when replicated chromosomes are separated into two new nuclei. Cell division gives rise to genetically identical cells in which the number of chromosomes is maintained. In general, mitosis is preceded by the S stage of interphase and is often accompanied or followed by cytokinesis, which divides the cytoplasm, organelles and cell membrane into two new cells containing roughly equal shares of these cellular components. Mitosis and cytokinesis together define the mitotic (M) phase of an animal cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.

Pom1 plays an important role in differentiating the old and new end of an S. pombe cell. Normal cell growth begins immediately in the old end of the cell and is delayed in the new end.^[3]pom1 mutants show immediate growth at both ends. Since Pom1 has been shown to be highly concentrated at the new end and nearly absent from the old end, it, along with other factors are part of an inhibitory signal that prevents immediate growth from the new end.^[1] Overexpression of Pom1 can also lead to the formation of new growth ends.^[3]

Pom1 is a relatively unique protein kinase as its closest homolog in S. pombe is only 55% identical. Homologs in other organisms include Dyrk in rats, Dyrk2 and Dyrk3 in humans, Yak1p in S. cerevisiae,^[4] and Minibrain in Drosophila and humans.^[1]^[5]

Saccharomyces cerevisiae is a species of yeast. It has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been originally isolated from the skin of grapes. It is one of the most intensively studied eukaryotic model organisms in molecular and cell biology, much like Escherichia coli as the model bacterium. It is the microorganism behind the most common type of fermentation. S. cerevisiae cells are round to ovoid, 5–10 μm in diameter. It reproduces by a division process known as budding.

Cell localization

During interphase, Pom1 resides throughout the cell including the medial cortical nodes. Pom1’s localization to the poles during cell division is regulated by Tea1 and Tea2.^[6]^[7] In the absence of Tea1 and Tea2, Pom1 maintains its kinase activity, but does not localize to the cell ends.^[3]^[7] Microtubules also help localize Pom1 in the cell as Pom1 delocalization has been shown to result from microtubule disassembly.^[1] Structurally, both the catalytic and non-catalytic regions of Pom1 are necessary for cell end localization.^[3]

Interphase part of the cell cycle after quiescent phase and before cell division

Interphase is the phase of the cell cycle in which a typical cell spends most of its life. During this phase, the cell copies its DNA in preparation for mitosis. Interphase is the 'daily living' or metabolic phase of the cell, in which the cell obtains nutrients and metabolizes them, grows, reads its DNA, and conducts other "normal" cell functions. The majority of eukaryotic cells spend most of their time in interphase. This phase was formerly called the resting phase. However, interphase does not describe a cell that is merely resting; rather, the cell is living, and preparing for later cell division, so the name was changed. A common misconception is that interphase is the first stage of mitosis. However, since mitosis is the division of the nucleus, prophase is actually the first stage.

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to the cytoplasm of eukaryotic cells, some bacteria and some archaea. A microtubule can grow as long as 50 micrometres and are highly dynamic. The outer diameter of a microtubule is about 24 nm while the inner diameter is about 12 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

The Cdr2, Cdr1, Wee1, Mid1, and Blt1 proteins are also located at the medial node during interphase and are believed to be part of the signaling pathway for mitotic entry.^[2]^[8] Cdr2 localization to the cell middle is regulated by the expression of Pom1 and other signals as pom1 mutants allow Cdr2 to diffuse from the medial node localization to one half of the cell.^[2]

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 it is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdk1. It has homologues in many other organisms, including mammals.

Cell Size and Spatial Gradient

Figure 1: Putative pathway for Pom1's regulation of mitotic entry. Pom1 suppresses Cdr2 that activates the Cdr1 and the suppression of Wee1. Suppressing Wee1 allows Cdk1 to help the cell enter mitosis. Pom1 Model.jpg — Figure 1: Putative pathway for Pom1's regulation of mitotic entry. Pom1 suppresses Cdr2 that activates the Cdr1 and the suppression of Wee1. Suppressing Wee1 allows Cdk1 to help the cell enter mitosis.

Pom1 forms a spatial gradient as cells elongate throughout G2 phase.^[2] Figure 1 illustrates in cartoon form the gradient of Pom1 (shown by the dark shading) across first a relatively small cell during interphase and an elongated cell passing through G2 phase. As cells elongate, Pom1 concentration peaks at the two poles and diminishes toward the center of the cell. Cdr2 reads the diminishing inhibitory signal from Pom1’s concentration gradient and activates Cdr1 and Blt1 that were localized at the medial node due to Cdr2 recruitment.^[2] Cdr1 then phosphorylates and inhibits Wee1, also recruited to the medial node by the presence of Cdr2.^[2] The phosphorylated Wee1 allows Cdc25 to dephosphorylate Cdk1 and move the cell into mitosis.^[2] Figure 2 depicts a simplified signaling pathway for size-dependent mitotic entry based on this model. The inhibition of Wee1 directly by Cdr2 shown by the dashed line has yet to be confirmed.

Tests of the Pom1 Model

Figure 2: Characterization of Pom1 localization at different points in the cell cycle. Pom1 is represented by the dark gray shading. White regions represent low concentrations of Pom1 after the cell has elongated and Pom1 localizes at the cell ends. Cell polarity.jpg — Figure 2: Characterization of Pom1 localization at different points in the cell cycle. Pom1 is represented by the dark gray shading. White regions represent low concentrations of Pom1 after the cell has elongated and Pom1 localizes at the cell ends.

GFP-tagged Pom1 has been shown to create a gradient in elongated cells as characterized in Figure 1. According to Figure 2, the decreased Pom1 at the location of Cdr2 in the medial node decreases the inhibition of Cdr2. In confirmation of this model’s interaction, results show that cells with delocalized Pom1 that retain full kinase activity from tea1 mutants delay mitotic entry. This is likely due to the continued inhibition of Cdr2.^[2] Further experiments that ectopically localized Pom1 throughout the cortex also showed delayed mitotic entry equivalent to a cdr2 knockdown suggesting once again that Pom1 inhibits Cdr2 and as Pom1 diminishes with cell elongation, Cdr2 begins a signaling pathway to inhibit Wee1 and eventually enter mitosis.^[2]

Future Research

It remains unclear if Cdr2 inhibits Wee1 directly or if it acts only indirectly through Cdr1 or other kinases. Furthermore, Blt1, also localized at the medial node, may play a role in mitotic entry regulation. Blt1 mutants show increased length consistent with delayed mitotic entry.^[2] Although currently unconfirmed, it is speculated that Blt1 acts by inhibiting Wee1.^[2]

Related Research Articles

Spindle apparatus the array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during mitosis or meiosis and serves to move the duplicated chromosomes apart.

In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.

The term cell growth is used in the contexts of biological cell development and cell division (reproduction). When used in the context of cell development, the term refers to increase in cytoplasmic and organelle volume, as well as increase in genetic material following the replication during S phase. This is not to be confused with growth in the context of cell division, referred to as proliferation, where a cell, known as the "mother cell", grows and divides to produce two "daughter cells".

Cyclin-dependent kinases (CDKs) are a family of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The consensus sequence for the phosphorylation site in the amino acid sequence of a CDK substrate is [S/T*]PX[K/R], where S/T* is the phosphorylated serine or threonine, P is proline, X is any amino acid, K is lysine, and R is arginine.

During the process of cell division, the spindle checkpoint prevents separation of the duplicated chromosomes until each chromosome is properly attached to the spindle apparatus. In order to preserve the cell's identity and proper function, it is necessary to maintain the appropriate number of chromosomes after each cell division. An error in generating daughter cells with fewer or greater number of chromosomes than expected, may lead in best case to cell death, or alternatively it may generate catastrophic phenotypic results. Examples include:

G₂ phase, or Gap 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.

Cdc25 is a dual-specificity phosphatase first isolated from the yeast Schizosaccharomyces pombe as a cell cycle defective mutant. As with other cell cycle proteins or genes such as Cdc2 and Cdc4, the "cdc" in its name refers to "cell division cycle". Dual-specificity phosphatases are considered a sub-class of protein tyrosine phosphatases. By removing inhibitory phosphate residues from target cyclin-dependent kinases (Cdks), Cdc25 proteins control entry into and progression through various phases of the cell cycle, including mitosis and S ("Synthesis") phase.

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 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. In humans, Cdk1 is encoded by the CDC2 gene. 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 fruit flies (Polo), budding yeast (Cdc5) and fission yeast (Plo1). Vertebrates, 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.

WEE1 homolog , also known as WEE1, is a protein which in humans is encoded by the WEE1 gene.

In biochemistry, a dual-specificity kinase is a kinase that can act as both tyrosine kinase and serine/threonine kinase.

Serine/threonine-protein kinase 13 is an enzyme that in humans is encoded by the AURKC gene.

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 ranging from yeast to mammals, ensuring that cells don't initiate mitosis until damaged DNA or incompletely replicated DNA is sufficiently repaired after replication. Cells that have a defective G2-M checkpoint enter mitosis before repairing their DNA, leading to apoptosis or death after cell division.

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. 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.

NDR kinases, are an ancient and highly conserved subclass of AGC protein kinases that control diverse processes related to cell morphogenesis, proliferation, and mitotic events.

The XMAP215/Dis1 family is a highly conserved group of microtubule-associated proteins (MAPs) in eukaryotic organisms. These proteins are unique MAPs because they primarily interact with the growing-end (plus-end) of microtubules. This special property classifies this protein family as plus-end tracking proteins (+TIPs).

Fus3 is a MAPK protein involved in the mating decision of yeast. The dissociation of Fus3 from scaffold protein Ste5 results in the switch-like mating decision observed in yeast. During this process, Fus3 competes with a phosphatase Pte1, attempting to phosphorylate 4 key phosphorylation sites on Ste5. When all 4 sites on Ste5 have been dephosphorylated by Pte1, Fus3 dissociates from Ste5 and trans locates to the nucleus.

References

1 2 3 4 5 6 Bahler, J., and Pringle, J.R. “Pom1p, a fission yeast protein kinase that provides positional information for both polarized growth and cytokinesis.” Genes and Development 12, 1356-1370 (1998).
1 2 3 4 5 6 7 8 9 10 11 Moseley, J.B., Mayeux, A., Paoletti, A. and Nurse, P. “A spatial gradient coordinates cell size and mitotic entry in fission yeast.” Nature 459, 857-861 (2009).
1 2 3 4 5 Bahler, J., and Nurse, P. “Fission yeast Pom1p kinase activity is cell cycle regulated and essential for cellular symmetry during growth and division.” The EMBO Journal 20, 1064-1073 (2001).
↑ Souza, G.M., Lu, S., and Kuspa, A. “YakA, a protein kinase required for the transition from growth to development in Dictyostelium. Development 125, 2291-2302 (1998).
↑ Tejedor, F., Zhu, X.R., Kaltenbach, E., Ackermann, A., Baumann, A., Canal, I., Heisenberg, M., Fischbach, K.F., and Pongs, O. “Minibrain: A new protein kinase family involved in postembryonic neurogenesis in Drosophila. Neuron 14, 287-301 (1995).
↑ Browning, H., Hayles, J., Mata, J., Aveline, L., Nurse, P. and McIntosh, J.R. “Tea2p is a kinesin-like protein required to generate polarized growth in fission yeast.” The Journal of Cell Biology 151,15-27 (2000).
1 2 Behrens, R., and Nurse, P. “Roles of fission yeast tea1p in the localization of polarity factors and in organizing the microtubular cytoskeleton.” The Journal of Cell Biology 157, 783-793 (2002).
↑ Morrell, J.L., Nichols, C.B., and Gould, K.L. “The GIN4 family kinase, Cdr2p, acts independently of septins in fission yeast. The Journal of Cell Science 117, 5293-5302 (2004).

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[bahler-1] 1 2 3 4 5 6 Bahler, J., and Pringle, J.R. “Pom1p, a fission yeast protein kinase that provides positional information for both polarized growth and cytokinesis.” Genes and Development 12, 1356-1370 (1998).

[moseley-2] 1 2 3 4 5 6 7 8 9 10 11 Moseley, J.B., Mayeux, A., Paoletti, A. and Nurse, P. “A spatial gradient coordinates cell size and mitotic entry in fission yeast.” Nature 459, 857-861 (2009).

[nurse-3] 1 2 3 4 5 Bahler, J., and Nurse, P. “Fission yeast Pom1p kinase activity is cell cycle regulated and essential for cellular symmetry during growth and division.” The EMBO Journal 20, 1064-1073 (2001).

[4] Souza, G.M., Lu, S., and Kuspa, A. “YakA, a protein kinase required for the transition from growth to development in Dictyostelium. Development 125, 2291-2302 (1998).

[5] Tejedor, F., Zhu, X.R., Kaltenbach, E., Ackermann, A., Baumann, A., Canal, I., Heisenberg, M., Fischbach, K.F., and Pongs, O. “Minibrain: A new protein kinase family involved in postembryonic neurogenesis in Drosophila. Neuron 14, 287-301 (1995).

[6] Browning, H., Hayles, J., Mata, J., Aveline, L., Nurse, P. and McIntosh, J.R. “Tea2p is a kinesin-like protein required to generate polarized growth in fission yeast.” The Journal of Cell Biology 151,15-27 (2000).

[Behrens,_R._2002-7] 1 2 Behrens, R., and Nurse, P. “Roles of fission yeast tea1p in the localization of polarity factors and in organizing the microtubular cytoskeleton.” The Journal of Cell Biology 157, 783-793 (2002).

[8] Morrell, J.L., Nichols, C.B., and Gould, K.L. “The GIN4 family kinase, Cdr2p, acts independently of septins in fission yeast. The Journal of Cell Science 117, 5293-5302 (2004).