Editing Maturation promoting factor

{{Refimprove|date=September 2014}}
'''Maturation-promoting factor''' (abbreviated '''MPF''', also called '''mitosis-promoting factor''' or '''M-Phase-promoting factor''') is  the [[Cyclin-dependent kinase complex|cyclin–Cdk complex]] that was discovered first in frog eggs.<ref name="Smith_1971">{{cite journal | vauthors = Smith LD, Ecker RE | title = The interaction of steroids with Rana pipiens Oocytes in the induction of maturation | journal = Developmental Biology | volume = 25 | issue = 2 | pages = 232–47 | date = June 1971 | pmid = 5562852 | doi = 10.1016/0012-1606(71)90029-7 }}</ref><ref name = "Masui_1971">{{cite journal | vauthors = Masui Y, Markert CL | title = Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes | journal = The Journal of Experimental Zoology | volume = 177 | issue = 2 | pages = 129–45 | date = June 1971 | pmid = 5106340 | doi = 10.1002/jez.1401770202 | bibcode = 1971JEZ...177..129M }}</ref>  It stimulates the [[mitotic]] and [[meiotic]] phases of the [[cell cycle]]. MPF promotes the entrance into mitosis (the M phase) from the [[G2 phase|G<sub>2</sub> phase]] by phosphorylating multiple proteins needed during mitosis. MPF is activated at the end of G<sub>2</sub> 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 [[L. Dennis Smith]] and Robert Ecker) found that frog [[oocyte]]s arrested in G<sub>2</sub> could be induced to enter M phase by microinjection of cytoplasm from oocytes that had been hormonally stimulated with progesterone.<ref name = "Masui_1971" /><ref name="Smith_1971" /> 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."<ref name="pmid6008374">{{cite journal | vauthors = Rusch HP, Sachsenmaier W, Behrens K, Gruter V | title = Synchronization of mitosis by the fusion of the plasmodia of Physarum polycephalum | journal = The Journal of Cell Biology | volume = 31 | issue = 1 | pages = 204–9 | date = October 1966 | pmid = 6008374 | pmc = 2107035 | doi = 10.1083/jcb.31.1.204 }}</ref>

== Structure ==
MPF is composed of two subunits: 
* [[Cyclin-dependent kinase 1]] (CDK1), the cyclin-dependent kinase subunit. It uses [[Adenosine triphosphate|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 G<sub>1</sub> and S phase, the CDK1 subunit of MPF is inactive due to an inhibitory enzyme, Wee1. Wee1 phosphorylates the Tyr-15 residue of CDK1, rendering MPF inactive. During the transition of G<sub>2</sub> 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. {{Clarify|date=November 2012}}

===Activation===
MPF must be activated in order for the cell to transition from G<sub>2</sub> to M phase. There are three amino acid residues responsible for this G<sub>2</sub> to M [[phase transition]]. The Threonine-161 (Thr-161) on CDK1 must be phosphorylated by a [[CDK-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.
* [[condensin]]s, which enable [[chromatin]] condensation (see [[prophase]])
* various [[microtubule]]-associated proteins involved in [[mitotic spindle]] formation
* [[lamin]]s, interaction contributing to degradation of the [[nuclear envelope]]
* Histones, H<sub>1</sub> and H<sub>3</sub>
* 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 ==
{{Reflist}}

{{Cell cycle proteins}}

[[Category:Protein complexes]]
[[Category:Cell cycle]]