MASTL

Last updated
MASTL
Identifiers
Aliases MASTL , GREATWALL, GW, GWL, MAST-L, THC2, hGWL, microtubule associated serine/threonine kinase like
External IDs OMIM: 608221 MGI: 1914371 HomoloGene: 12086 GeneCards: MASTL
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_025979

RefSeq (protein)

NP_080255

Location (UCSC) Chr 10: 27.15 – 27.19 Mb Chr 2: 23.01 – 23.05 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

Micro-tubule-associated serine/threonine protein kinase is a mammalian enzyme which was first discovered in Drosophila as an essential kinase (great wall) for correct chromosome condensation and mitotic progression. The EC number for this enzyme is 2.7.11.12. This enzyme is active during mitotic division and is mainly localized in the nucleus during interphase. They get dispersed into the cytoplasm upon the degradation of nuclear envelope during mitosis. The MASTL depleted cells are delayed by RNAi in G2 phase and show a decreased condensation of the chromosomes. RNAi cells which pass through the mitosis, might not get separated into their sister chromatids in anaphase. This causes the chromatin to be trapped in the cleavage furrow and form 4N G1 cells due to cytokinesis failure. This enzyme enhances the cyclin B1-Cdk1-dependent mitotic phosphorylation events during mitosis. [5]

Although Mastl kinase is not essential for metaphase entry, it is required for its maintenance by sustaining spindle assembly checkpoint signaling. [6] Suppression of protein phosphatase 2A activity by Mastl/Arpp19/ENSA pathway leads to sustained high level of Cdk1 substrate phosphorylation until anaphase. It also provides the timely activation of APC/C during Meiosis I and Cdk1 reactivation in meiosis II. [7]

Mutation in the gene

A missense mutation in the MASTL gene can lead to an autosomal dominant inherited thrombocytopenia. The mutation is due to the change in amino acid glutamic acid at 167 to aspartic acid. Common phenotype of a mild thrombocytopenia patient is the decrease average plate counts of 60,000 platelets per ml of blood.

Uses in the therapeutic field

MASTL enzyme is also used for therapeutic applications such as cancer progression and tumor recurrence after free cancer therapy and this enzyme can be of higher value in the therapeutic market. [8]


Related Research Articles

<span class="mw-page-title-main">Meiosis</span> Type of cell division in sexually-reproducing organisms used to produce gametes

Meiosis is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and female will fuse to create a cell with two copies of each chromosome again, the zygote.

<span class="mw-page-title-main">Mitosis</span> Process in which replicated chromosomes are separated into two new identical nuclei

In cell biology, mitosis is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintained. Therefore, mitosis is also known as equational division. In general, mitosis is preceded by S phase 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 altogether 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.

<span class="mw-page-title-main">Cell division</span> Process by which living cells divide

Cell division is the process by which a parent cell divides, when a mother cell divides into two or more daughter cells. Cell division usually occurs as part of a larger cell cycle. In eukaryotes, there are two distinct types of cell division; a vegetative division, whereby each daughter cell is genetically identical to the parent cell (mitosis), and a reproductive cell division, whereby the number of chromosomes in the daughter cells is reduced by half to produce haploid gametes (meiosis). 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 results in four haploid daughter cells by undergoing one round of DNA replication followed by two divisions. Homologous chromosomes are separated in the first division, and sister chromatids are separated in the second division. 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.

<span class="mw-page-title-main">Cell growth</span> Increase in the total cell mass

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.

<span class="mw-page-title-main">Spermatocyte</span> Sperm precursor cell that undergoes meiosis

Spermatocytes are a type of male gametocyte in animals. They derive from immature germ cells called spermatogonia. They are found in the testis, in a structure known as the seminiferous tubules. There are two types of spermatocytes, primary and secondary spermatocytes. Primary and secondary spermatocytes are formed through the process of spermatocytogenesis.

Endoreduplication is replication of the nuclear genome in the absence of mitosis, which leads to elevated nuclear gene content and polyploidy. Endoreplication can be understood simply as a variant form of the mitotic cell cycle (G1-S-G2-M) in which mitosis is circumvented entirely, due to modulation of cyclin-dependent kinase (CDK) activity. Examples of endoreplication characterized in arthropod, mammalian, and plant species suggest that it is a universal developmental mechanism responsible for the differentiation and morphogenesis of cell types that fulfill an array of biological functions. While endoreplication is often limited to specific cell types in animals, it is considerably more widespread in plants, such that polyploidy can be detected in the majority of plant tissues.

<span class="mw-page-title-main">Aurora kinase A</span> Protein-coding gene in the species Homo sapiens

Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.

<span class="mw-page-title-main">Aurora kinase B</span> Protein

Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.

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.

<span class="mw-page-title-main">PLK1</span>

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.

<span class="mw-page-title-main">CDC20</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">BUB1</span>

Mitotic checkpoint serine/threonine-protein kinase BUB1 also known as BUB1 is an enzyme that in humans is encoded by the BUB1 gene.

<span class="mw-page-title-main">BUB1B</span>

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene.

<span class="mw-page-title-main">Cell division cycle 7-related protein kinase</span> Protein-coding gene in the species Homo sapiens

Cell division cycle 7-related protein kinase is an enzyme that in humans is encoded by the CDC7 gene. The Cdc7 kinase is involved in regulation of the cell cycle at the point of chromosomal DNA replication. The gene CDC7 appears to be conserved throughout eukaryotic evolution; this means that most eukaryotic cells have the Cdc7 kinase protein.

<span class="mw-page-title-main">Centromere protein E</span> Centromere- and microtubule-associated protein

Centromere-associated protein E is a protein that in humans is encoded by the CENPE gene.

<span class="mw-page-title-main">NEK6</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase Nek6 is an enzyme that in humans is encoded by the NEK6 gene.

<span class="mw-page-title-main">Aurora kinase C</span> Protein-coding gene in the species Homo sapiens

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

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.

<span class="mw-page-title-main">NEK8</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase Nek8, also known as never in mitosis A-related kinase 8, is an enzyme that in humans is encoded by the NEK8 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000120539 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026779 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Voets; Wolthuis (2010). "MASTL is the human ortholog of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis". Cell Cycle. 9 (17): 3591–3601. doi: 10.4161/cc.9.17.12832 . PMID   20818157.
  6. Diril; Bisteau; Kitagawa (2016). "Loss of the Greatwall kinase weakens the spindle assembly checkpoint". PLOS Genetics. 12 (9): e1006310. doi:10.1371/journal.pgen.1006310. PMC   5025047 . PMID   27631493. S2CID   36386949.
  7. Adhikari; Diril; Busayavalasa (2014). "Mastl is required for timely activation of APC/C in meiosis I and Cdk1 reactivation in meiosis II" (PDF). J Cell Biol. 206 (7): 843–853. doi: 10.1083/jcb.201406033 . PMC   4178961 . PMID   25246615. S2CID   11425498.
  8. Wang; Luong; Giannini; Peng (2014). "Mastl kinase, a promising therapeutic target, promotes cancer recurrence". Oncotarget. 5 (22): 11479–11489. doi:10.18632/oncotarget.2565. PMC   4294390 . PMID   25373736.

Further reading