同: MPF

WordNet

be a contributing factor; "make things factor into a companys profitability"
any of the numbers (or symbols) that form a product when multiplied together
an independent variable in statistics
anything that contributes causally to a result; "a number of factors determined the outcome"
consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
a concept whose truth can be proved; "scientific hypotheses are not facts"
a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
coming to full development; becoming mature (同)ripening, maturement

PrepTutorEJDIC

(…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
成熟,円熟

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2019/09/16 20:12:07」(JST)

wiki en

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.^[1]^[2] 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.

The MPF is also called the M phase kinase because of its ability to phosphorylate target proteins at a specific point in the cell cycle and thus control their ability to function.

Discovery

In 1971, two independent teams of researchers (Yoshio Masui and Clement Markert, as well as Dennis Smith and Robert Ecker) found that frog oocytes arrested in G₂ could be induced to enter M phase by microinjection of cytoplasm from oocytes that had been hormonally stimulated with progesterone.^[2]^[1] Because the entry of oocytes into meiosis is frequently referred to as oocyte maturation, this cytoplasmic factor was called maturation promoting factor (MPF). Further studies showed, however, that the activity of MPF is not restricted to the entry of oocytes into meiosis. To the contrary, MPF is also present in somatic cells, where it induces entry into M phase of the mitotic cycle.

Evidence that a diffusible factor regulates the entry into mitosis had been previously obtained in 1966 using the slime mold Physarum polycephalum in which the nuclei of the multi-nucleate plasmodial form undergo synchronous mitoses. Fusing plasmodia whose cell cycles were out of phase with each other led to a synchronous mitosis in the next mitotic cycle. This result demonstrated that mitotic entry was controlled by a diffusible cytoplasmic factor and not by a "nuclear clock."^[3]

Structure

MPF is composed of two subunits:

Cyclin-dependent kinase 1 (CDK1), the cyclin-dependent kinase subunit. It uses ATP to phosphorylate specific serine and threonine residues of target proteins.
Cyclin, a regulatory subunit. The cyclins are necessary for the kinase subunit to function with the appropriate substrate. The mitotic cyclins can be grouped as cyclins A & B. These cyclins have a nine residue sequence in the N-terminal region called the “destruction box”, which can be recognized by the ubiquitin ligase enzyme which destroys the cyclins when appropriate.

Role in the cell cycle

During G₁ and S phase, the CDK1 subunit of MPF is inactive due to an inhibitory enzyme, Wee1. Wee1 phosphorylates the Thr-14 residues in yeast and Tyr-15 residues in humans of CDK1, rendering MPF inactive. During the transition of G₂ to M phase, cdk1 is de-phosphorylated by CDC25. The CDK1 subunit is now free and can bind to cyclin B, activate MPF, and make the cell enter mitosis. There is also a positive feedback loop that inactivates wee1.^{[clarification needed]}

Activation

MPF must be activated in order for the cell to transition from G₂ to M phase. There are three amino acid residues responsible for this G₂ to M phase transition. The Threonine-161 (Thr-161) on CDK1 must be phosphorylated by a Cyclin Activating Kinase (CAK). CAK only phosphorylates Thr-161 when cyclin B is attached to CDK1.

In addition, two other residues on the CDK1 subunit must be activated by dephosphorylation. CDC25 removes a phosphate from residues Threonine-14 (Thr-14) and Tyrosine-15 (Tyr-15) and adds a hydroxyl group. Cyclin B/CDK1 activates CDC25 resulting in a positive feedback loop.

Overview of functions

Triggers the formation of mitotic spindle through microtubule instability.
Promotes mitosis i.e. chromatin condensation through phosphorylation of condensins.
The three lamins present in the nuclear lamina, lamin A, B & C, are phosphorylated by MPF at serine amino residues. This leads to depolymerisation of the nuclear lamina & breakdown of nuclear envelope into small vesicles.
Causes phosphorylation of GM130, which leads to the fragmentation of the Golgi and the ER

Targets

The following are affected by MPF.

condensins, which enable chromatin condensation (see prophase)
various microtubule-associated proteins involved in mitotic spindle formation
lamins, interaction contributing to degradation of the nuclear envelope
Histones, H₁ and H₃
Golgi matrix, to cause fragmentation

Inhibition of myosin

MPF phosphorylates inhibitory sites on myosin early in mitosis. This prevents cytokinesis. When MPF activity falls at anaphase, the inhibitory sites are dephosphorylated and cytokinesis proceeds.

Disassembly by anaphase-promoting complex

MPF is disassembled when anaphase-promoting complex (APC) polyubiquitinates cyclin B, marking it for degradation in a negative feedback loop. In intact cells, cyclin degradation begins shortly after the onset of anaphase (late anaphase), the period of mitosis when sister chromatids are separated and pulled toward opposite spindle poles. As the concentration of Cyclin B/CDK1 increases, the heterodimer promotes APC to polyubiquitinate Cyclin B/CDK1.

References

^ ^a ^b Smith LD, Ecker RE (June 1971). "The interaction of steroids with Rana pipiens Oocytes in the induction of maturation". Developmental Biology. 25 (2): 232–47. doi:10.1016/0012-1606(71)90029-7. PMID 5562852.
^ ^a ^b Masui Y, Markert CL (June 1971). "Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes". The Journal of Experimental Zoology. 177 (2): 129–45. doi:10.1002/jez.1401770202. PMID 5106340.
^ Rusch HP, Sachsenmaier W, Behrens K, Gruter V (October 1966). "Synchronization of mitosis by the fusion of the plasmodia of Physarum polycephalum". The Journal of Cell Biology. 31 (1): 204–9. doi:10.1083/jcb.31.1.204. PMC 2107035. PMID 6008374.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 骨髄造血の制御 regulation of myelopoiesis
2. 血友病患者における第VIIIおよび第IX因子阻害物質 factor viii and factor ix inhibitors in patients with hemophilia
3. 非血友病患者における遺伝子組換え第VIIa凝固因子の治療使用 therapeutic uses of recombinant coagulation factor viia in non hemophiliacs
4. von Willebrand因子の生物学および正常機能 biology and normal function of von willebrand factor
5. 血管新生阻害剤の概要 overview of angiogenesis inhibitors

English Journal

Apoptosis in mammalian oocytes: a review.

Tiwari M1, Prasad S, Tripathi A, Pandey AN, Ali I, Singh AK, Shrivastav TG, Chaube SK.
Apoptosis : an international journal on programmed cell death.Apoptosis.2015 Aug;20(8):1019-25. doi: 10.1007/s10495-015-1136-y.
Apoptosis causes elimination of more than 99 % of germ cells from cohort of ovary through follicular atresia. Less than 1 % of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species includi
PMID 25958165

Role of arachidonic acid cascade in Rhinella arenarum oocyte maturation.

Ortiz ME1, Arias-Torres AJ2, Zelarayán LI3.
Zygote (Cambridge, England).Zygote.2015 Aug;23(4):603-14. doi: 10.1017/S0967199414000240. Epub 2014 Jun 25.
There are no studies that document the production of prostaglandins (PGs) or their role in Rhinella arenarum oocyte maturation. In this study, we analysed the effect of arachidonic acid (AA) and prostaglandins (PGs) on maturation, activation and pronuclear formation in R. arenarum oocytes. Our resul
PMID 24964276

Defective Guanine Nucleotide Exchange in the Elongation Factor-like 1 (EFL1) GTPase by Mutations in the Shwachman-Diamond Syndrome Protein.

García-Márquez A1, Gijsbers A1, de la Mora E1, Sánchez-Puig N2.
The Journal of biological chemistry.J Biol Chem.2015 Jul 17;290(29):17669-78. doi: 10.1074/jbc.M114.626275. Epub 2015 May 19.
Ribosome biogenesis is orchestrated by the action of several accessory factors that provide time and directionality to the process. One such accessory factor is the GTPase EFL1 involved in the cytoplasmic maturation of the ribosomal 60S subunit. EFL1 and SBDS, the protein mutated in the Shwachman-Di
PMID 25991726