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Question

Following statements were made about cell cycle regulation in eukaryotes:

A. Activity of maturation promoting factor (MPF) rises and falls in synchrony with the concentration of cyclin B.

B. Cdc25 phosphatase mediates removal of phosphate from the inhibitory tyrosine residue (Y15) to yield highly active MPF.

C. MPF specifically phosphorylates and depolymerizes lamin A and C, but not lamin B.

D. MPF phosphorylates H1 histone.

E. In Schizosaccharomyces pombe, overproduction of Wee1 protein decreases the length of G2 phase and extends the period of M phase by functioning as a mediator of MPF activity.

Which one of the following represents the combination of correct statements?

The correct answer is

A, B and D

Cell Cycle Regulation and MPF in Eukaryotes

Cell cycle regulation in eukaryotic cells is a complex process controlled by various proteins, most notably Cyclin-Dependent Kinases (CDKs) in association with cyclins. Maturation Promoting Factor (MPF) is a key regulator, specifically driving the cell from G2 phase into mitosis (M phase).

Understanding MPF and its Components

MPF is primarily composed of two subunits: a catalytic subunit, which is a CDK (specifically Cdk1, also known as Cdc2 in some organisms like yeast), and a regulatory subunit, which is a cyclin (specifically cyclin B).

Statement Analysis

Statement A: MPF Activity and Cyclin B

Statement A says: "Activity of maturation promoting factor (MPF) rises and falls in synchrony with the concentration of cyclin B."

This statement is correct. Cyclin B is synthesized during the interphase (G2) and accumulates. This accumulation leads to the formation of the active MPF complex (Cdk1-Cyclin B). As mitosis progresses and the cell prepares to exit M phase, cyclin B is rapidly degraded by the ubiquitin-proteasome system. The degradation of cyclin B causes the drop in MPF activity, which is essential for the cell to exit mitosis and enter G1 phase. Therefore, MPF activity closely follows the concentration profile of cyclin B.

Statement B: Cdc25 Phosphatase and MPF Activation

Statement B says: "Cdc25 phosphatase mediates removal of phosphate from the inhibitory tyrosine residue (Y15) to yield highly active MPF."

This statement is correct. Cdk1 (the catalytic subunit of MPF) activity is regulated by phosphorylation. Specifically, it is inhibited by phosphorylation on tyrosine 15 (Y15) and threonine 14 (T14), primarily by kinases like Wee1. To become fully active, these inhibitory phosphates must be removed. The enzyme responsible for removing these phosphates is Cdc25 phosphatase. Cdc25 removes the phosphate from Y15 (and T14), leading to the activation of the Cdk1/Cyclin B complex, i.e., MPF. Thus, Cdc25 is crucial for MPF activation and entry into mitosis.

Statement C: MPF and Nuclear Lamins

Statement C says: "MPF specifically phosphorylates and depolymerizes lamin A and C, but not lamin B."

This statement is incorrect. During mitosis, the nuclear envelope breaks down. This process is triggered by MPF-mediated phosphorylation of the proteins that form the nuclear lamina, which is a meshwork supporting the nuclear envelope. The nuclear lamina is composed of lamins, including lamin A, lamin B, and lamin C. MPF phosphorylates all types of nuclear lamins (lamin A, lamin B, and lamin C), leading to their depolymerization and the breakdown of the nuclear envelope. The statement incorrectly claims that lamin B is not phosphorylated.

Statement D: MPF and H1 Histone

Statement D says: "MPF phosphorylates H1 histone."

This statement is correct. Histone H1 is a linker histone that helps compact chromatin. Phosphorylation of histone H1 by MPF is one of the events that contributes to the extensive chromatin condensation observed during mitosis. This phosphorylation alters the interaction between H1 and DNA, facilitating chromosome condensation.

Statement E: Wee1 Protein in Schizosaccharomyces pombe

Statement E says: "In Schizosaccharomyces pombe, overproduction of Wee1 protein decreases the length of G2 phase and extends the period of M phase by functioning as a mediator of MPF activity."

This statement is incorrect. Wee1 is a kinase that inhibits Cdk1 (Cdc2 in S. pombe) by phosphorylating it at the inhibitory tyrosine residue (Y15). Overproduction of Wee1 would lead to increased inhibitory phosphorylation of Cdk1. This would delay the activation of MPF, thereby *extending* the G2 phase (the period before mitosis) and delaying entry into M phase, not decreasing the length of G2. Furthermore, Wee1 inhibits MPF activity; it does not mediate its activity in the sense of promoting it.

Summary of Correct Statements

Based on the analysis:

  • Statement A is correct.
  • Statement B is correct.
  • Statement C is incorrect.
  • Statement D is correct.
  • Statement E is incorrect.

The combination of correct statements is A, B, and D.

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Important Questions from Cell Division and Cell Cycle

  1. During cell cycle, entry in the S-phase is tightly regulated. This is possible because:

    A. APC/C promotes ubiquitination of S-phase cyclins and mitotic cyclins, marking them for proteolyses at the mitotic exit.

    B. Cyclin B1 helps in the activation of S-phase CDKs only in late G1.

    C. As mitotic CDK activity declines in late mitosis, cdc14 phosphatase activates APC/C by dephosphorylating Cdh1, thus promoting formation of APC/CCdh1

    D. Securin keeps S-phase cyclins in inactive state till late G1.

    Which one of the options represents all correct statements?

  2. Following statements were made about cell cycle regulation:

    A. De novo synthesis and destruction of Cyclin B are essential for cell cycle progression in yeast.

    B. De novo synthesis and destruction of Cyclin B and the related Cyclin dependent Kinase (CDK) are essential for cell cycle progression.

    C. CDK activity is regulated by both activating and inhibitory phosphorylation.

    D. Retinoblastoma (Rb) functions as an inhibitor of G2 to M transition.

    E. Inactivation of Sic 1 is essential for transition into S phase.

    Which one of the following represents the combination of the correct statements?

  3. The table below lists cell cycle regulatory proteins and their known functions

    Cell Cycle regu latory proteinsFunction
    A Cdk-activating kinase (CAK)(i)Suppresses G1/S-Cdk and S-Cdk  activation in G1; helps cells withdraw  from cell cycle when they terminally  differentiate; phosphorylation by Cdk2  triggers its ubiquitylation by SCF.
    BWee1 kinase(ii)Suppresses G1/S-Cdk and S-Cdk  activities following DNA damage
    Cp27 (mammals)(iii) Phosphorylates inhibitory sites in  Cdks: primarily involved in  suppressing Cdk1 activity before  mitosis
    Dp21 (mammals)(iv)Phosphorylates an activating site in  Cdks
    Which one of the following options represents the correct match  between cell cycle regulatory proteins with their known functions?
  4. Following statements were made about the characteristics of cyclin proteins:

    A. Synthesis of M-cyclin is dependent on the cyclin mRNA that is newly transcribed after every cycle.

    B. Destruction of M-cyclin toward the end of mitosis is driven by ubiquitin independent proteolytic system.

    C. G1 cyclins can be activated by mitogenic factors.

    D. Retinoblastoma (Rb) is a key target of the activated cyclin D - Cdk 4/6 complex.

    E. While cyclin A1 expression is ubiquitous, cyclin A2 expression is restricted to the germ cell lineages.

    Which one of the following options contains a combination of all correct statements?

  5. To test the impact of cAMP on protein kinase A conformation in cells, an investigator made FRET biosensor by fusing two fluorescent proteins at the N-and C-terminus of protein kinase A. In the absence of cAMP in the cellular milieu, no FRET signal was detected. However, upon cAMP addition, a strong emission at 530 nm was observed. What could be the best configuration of fluorophores that were used by the investigator?

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