Pom1
Encyclopedia
Pom1 is a polarity protein kinase
in fission yeast, S. pombe, that localizes to cell ends. The gene
pom1 codes for a protein 1087 amino acids long with the protein kinase
domain likely located at the carboxyl terminus. Pom1 regulates a signaling pathway that includes Cdk1
and ultimately regulates mitotic entry
. 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.
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. pom1 mutants show immediate growth at either end. 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. Overexpression of Pom1 can also lead to the formation of new growth ends.
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
, and Minibrain in Drosophila and humans.
, 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. In the absence of Tea1 and Tea2, Pom1 maintains its kinase
activity, but does not localize to the cell ends. Microtubules also help localize Pom1 in the cell as Pom1 delocalization has been shown to result from microtubule
disassembly. Structurally, both the catalytic and non-catalytic regions of Pom1 are necessary for cell end localization.
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. 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.
. 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. Cdr1 then phosphorylates and inhibits Wee1
, also recruited to the medial node by the presence of Cdr2. The phosphorylated Wee1
allows Cdc25
to dephosphorylate Cdk1
and move the cell into mitosis
. 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.
activity from tea1 mutants delay mitotic entry. This is likely due to the continued inhibition of Cdr2. 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
.
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. Although currently unconfirmed, it is speculated that Blt1 acts by inhibiting Wee1
.
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
in fission yeast, S. pombe, that localizes to cell ends. The gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
pom1 codes for a protein 1087 amino acids long with the protein kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
domain likely located at the carboxyl terminus. Pom1 regulates a signaling pathway that includes Cdk1
Cdk1
Cyclin dependent kinase 1 also known as Cdk1 or cell division control 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....
and ultimately regulates mitotic entry
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
. 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.
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. pom1 mutants show immediate growth at either end. 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. Overexpression of Pom1 can also lead to the formation of new growth ends.
Pom1 is a relatively unique protein kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
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
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
, and Minibrain in Drosophila and humans.
Cell Localization
During interphaseInterphase
Interphase is the phase of the cell cycle in which the cell spends the majority of its time and performs the majority of its purposes including preparation for cell division. In preparation for cell division, it increases its size and makes a copy of its DNA...
, 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. In the absence of Tea1 and Tea2, Pom1 maintains its kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
activity, but does not localize to the cell ends. Microtubules also help localize Pom1 in the cell as Pom1 delocalization has been shown to result from microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
disassembly. Structurally, both the catalytic and non-catalytic regions of Pom1 are necessary for cell end localization.
The Cdr2, Cdr1, Wee1
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe . It has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression....
, Mid1, and Blt1 proteins are also located at the medial node during interphase
Interphase
Interphase is the phase of the cell cycle in which the cell spends the majority of its time and performs the majority of its purposes including preparation for cell division. In preparation for cell division, it increases its size and makes a copy of its DNA...
and are believed to be part of the signaling pathway for mitotic entry. 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.
Cell Size and Spatial Gradient
Pom1 forms a spatial gradient as cells elongate throughout G2 phaseG2 phase
G2 phase is the 3rd and final 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...
. Figure 1 illustrates in cartoon form the gradient of Pom1 (shown by the dark shading) across first a relatively small cell during interphase
Interphase
Interphase is the phase of the cell cycle in which the cell spends the majority of its time and performs the majority of its purposes including preparation for cell division. In preparation for cell division, it increases its size and makes a copy of its DNA...
and an elongated cell passing through G2 phase
G2 phase
G2 phase is the 3rd and final 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...
. 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. Cdr1 then phosphorylates and inhibits Wee1
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe . It has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression....
, also recruited to the medial node by the presence of Cdr2. The phosphorylated Wee1
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe . It has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression....
allows Cdc25
Cdc25
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 such as Cdc2 and Cdc4, the "cdc" in its name refers to "cell division cycle".Dual-specificity phosphatases are considered a sub-class...
to dephosphorylate Cdk1
Cdk1
Cyclin dependent kinase 1 also known as Cdk1 or cell division control 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....
and move the cell into mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
. Figure 2 depicts a simplified signaling pathway for size-dependent mitotic entry based on this model. The inhibition of Wee1
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe . It has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression....
directly by Cdr2 shown by the dashed line has yet to be confirmed.
Tests of the Pom1 Model
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 kinaseKinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
activity from tea1 mutants delay mitotic entry. This is likely due to the continued inhibition of Cdr2. 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
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe . It has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression....
and eventually enter mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
.
Future Research
It remains unclear if Cdr2 inhibits Wee1Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe . It has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression....
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. Although currently unconfirmed, it is speculated that Blt1 acts by inhibiting Wee1
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe . It has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression....
.