Mitosis promoting factor

Unfortunately, this field is made difficult for a student by the terminology used by biochemists. For example, there is a protein kinase that regulates the cycle between G2 and M, i.e. the second restriction point. This protein is known as maturation (or mitosis) promoting factor, since it promotes entry into mitosis. It phosphorylates a protein, probably a transcription factor, in the nucleus. The kinase has a molecular mass of 34kDa. Hence it is known as p34 cell division kinase, abbreviated to p34-cdc and, since it is regulated at restriction point 2, it is known as p34-cdc-2 protein, which is sometimes written as p34°. This kinase is normally inactive until it binds a cyclin. Hence the active maturation-promoting factor is, in fact, a protein kinase-cyclin complex, which is referred to as p34° °-cyclin complex. It is hoped that this piece of information may help a student (or lecturer from another field) to understand one part of a review article that contains the abbreviation p34° -cyclin complex, without explanation, or other similar pieces of biochemical shorthand. 

Entry of animal cells into mitosis is based on the mitosis-promoting factor (MPF). MPF consists of CDK1 (cdc2) and cyclin B. The intracellular concentration of cyclin B increases constantly until mitosis starts, and then declines again rapidly (top left). MPF is initially inactive, because CDKl is phosphorylated and cyclin B is dephosphorylated (top center). The M phase is triggered when a protein phosphatase [1] dephosphorylates the CDK while cyclin B is phosphorylated by a kinase [2]. in its active form, MPF phosphorylates various proteins that have functions in mitosis—e.g., histone HI (see p. 238), components of the cytoskeleton such as the laminins in the nuclear membrane, transcription factors, mitotic spindle proteins, and various enzymes. 

Entry into and the course of mitosis are primarily determined by the activity of the CDC2 kinase. The CDC2 kinase in the active form exists as a complex with cychn B and, together with the cyclin, forms the mitosis promoting factor, MPF. The activity of MPF oscillates in the cell cycle and is the triggering factor for entry of the cell into M phase. 

Bruggemann A, Stiihmer W, Pardo LA (1997) Mitosis-promoting factor-mediated suppression of a cloned delayed rectifier potassium channel expressed in Xenopus oocytes. Proc Natl Acad Sci USA 94 537-542... 

Entry into M phase is primarily determined by the activity of the cyclin B-CDC2 kinase complex, which is also called the mitosis-promoting factor, MPF. 

Those cyclins and CDKs discussed in this chapter are listed and classified by the period in the cell cycle in which they function. A heterodimer composed of a mitotic cyclin and CDK is commonly referred to as a mitosis-promoting factor (MPF). 

Cyclin B Levels and Kinase Activity of Mitosis-Promoting Factor (MPF) Change Together in Cycling Xenopus Egg Extracts... 

By the late 1980s, It was clear that mitosis-promoting factor (MPF) is composed of two subunits a CDK and a mitotic... 

Interphase 854 meiosis 890 mitogens 856 mitosis-promoting factor (MPF) 860 mitotic cyclln 861 p53 protein 889 quiescent cells 883 Rb protein 884 restriction point 883 S-phase inhibitor 868 S phase-phase promoting factor (SPF) 876 securln 872 synapsis 892 Weel protein-tyrosine kinase 866... 

In amphibian eggs (fig. 10.2), the cell cycle has a simple form as it consists in the periodic alternation of mitosis and interphase. Mitosis is associated with the activation of a factor known as maturation (or mitosis) promoting factor (MPF). Activation of MPF is triggered by the building up to a threshold of cyclin, a protein whose name reflects its... 

Fig. 10.2. (a) The early amphibian embryonic cell cycle, (b) Role of maturation (or mitosis)-promoting factor (MPF) and cyclin in the periodic alternation of interphase and mitosis in that cycle, ((a) reproduced from Murray, 1989b (b) reproduced from Minshull et al, 1989). 

Cyclin B/CDKl is the primary regulator of the G2/M transition, and its activity is required for entry into mitosis. It was termed the maturation-promoting factor (MPF) because it was originally shown to be essential for Xenopus oocytes maturation... 

Maturation-Promoting Factor (MPF) Stimulates Meiotic Maturation of Oocytes and Mitosis in Somatic Cells... 

These toxins can influence the cell cycle by a complex series of direct and indirect actions on a variety of molecular targets by inhibiting protein phosphatases, hence altering the phosphorylation state of proteins involved in the control of the cell cycle. Exposine of mammalian cells to OA leads to hyperphosphorylation and activation of cyclin-dependent kinase 1-cyclin B complex (CDKl-cyc-lin B, called also M-phase-promoting factor, MPF or Cdc2-cyclin B), which leads the cells to G2/M transition and to a mitosis-like state, characterized by a premature chromosome condensation and break of the nuclear lamina. This event seems to depend mainly on the inhibition of protein phosphatase 2A, which is necessary to maintain the complex CDKl-cydin B in its inactive form. Nevertheless, inhibition of other phosphatases, such as protein phosphatases 4 and 5, could mediate. 

Grieco D, Porcellini A, Avvedimento EV, Gottesman ME. 1996. Requirement for cAMP-PKA pathway activation by M phase-promoting factor in the transition from mitosis to interphase. Science 271(5256) 1718-1723. 

HCH is the major pesticide used to control pest hazards all over the world. O -HCH is chiral, while the y-isomer is achiral but its decomposition results in chiral pentachlorocyclohexene (PCCB) metabolite. Several reports have been published on the enantioselective accumulation of a-HCH pesticides (Chapter 2). Therefore, it is obvious that the biochemistry of a-HCH enantiomers is different. In spite of this, little work has been carried out to determine the enantioselective toxicities of the HCH isomers. Moller et al. [24] observed different toxicities of a-HCH enantiomers on cytotoxicity and growth stimulation in primary rat hepatocytes. The cytotoxic effect was determined as a parameter for the acute toxicity of a-HCH, while the growth stimulation may be associated with chronic toxicity for example, the promotion of tumours. The authors cultured hepatocytes separately in the presence of (-1-)- and (—)-a-HCH pesticides, and reported 100% mortality in the presence of 3 x 10 " M (-l-)-a-HCH, while at the same concentration of (—)-a-HCH, 75% mortality was reported. Furthermore, the authors reported no toxic effects of (—)-a-HCH at a lower concentration (1 X 10 " M), while the mortality rate was 62% at this concentration of (-l-)-a-HCH enantiomer. The authors also studied the mimetic rates of a-HCH enantiomers in rats. 5 x 10 M concentrations of both of the enantiomers were injected separately into rats, and it was observed that the significant mitosis occurred (factor 2.4) in the presence of the (-h)-a-HCH enantiomer, as compared with stimulation by the (—)-a-HCH enantiomer (factor 1.7). Therefore, it may be concluded, from the study carried out by Moller et al. [24], that the (-l-)-enantiomer of a-HCH is more toxic than the (—)-enantiomer. The mortality in primary cultures of rat hepatocytes as a function of the (- -)- and (—)-a-HCH concentrations and the stimulation... 

Direct inhibition of the formation of a pre-initiation complex complexation of basal transcription factors, such as TFIID or TFIIB, or competition with TFIIB for binding to the promoter. An example for this type of repression is the negative cofactor NC2 (see 1.4.3.2). Transcription repression can also result from phosphorylation of the basal transcription factors. By this token, the repression of transcription observed during mitosis is attributed to the hyperphosphorylation of TBP and TAFs. 

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