Question

Cyclin and Cdk proteins control the cell cycle, with different combinations of cyclins and Cdks being activated at different times in the cycle. How does the combination of adding and removing phosphates regulate M cyclin-Cdk complex activity?

Answer 1

Cell Cycle Control

A “clock” is running within the cell - of synthesis and degradation of cyclins - which activate cyclin-dependant kinases (Cdk’s), which activate other proteins to cause checkpoint transitions.

Regulation of the Cell Cycle: Cell Cycle Checkpoints

1. G2 Checkpoint Control by MPF
2. Active MPF = Mitotic Cdk + mitotic cyclin
3. Cdk is cyclin-dependant kinase
4. MPF controls G2
5. M by phosphorylating and activating proteins involving in: Chromosome condensation Nuclear envelope breakdown Spindle assembly It’s own self-destruction

G1 checkpoint

1. Controlled by G1 Cdks-cyclin
2. G1 cyclin levels also vary with the cell cycle
3. Many additional levels of phosphorylation, dephosphorylation regulate.

The Cell Cycle Regulation by Protein Kinases.

1. The mechanism regulating the progression of cells through their division cycle is highly conserved in evolution, and plants have retained the basic components of this mechanism.
2. The key enzymes that control the transitions between the different states of the cell cycle, and the entry of nondividing cells into the cell cycle, are the cyclin-dependent protein kinases, or CDKs
3. Protein kinases are enzymes that phosphorylate proteins using ATP.
4. The regulated activity of CDKs is essential for the transitions from G1 to S and from G2 to M, and for the entry of nondividing cells into the cell cycle.
5. The transition from G1 to S requires a set of cyclins ( G1 cyclins) different from those required in the transition from G2 to mitosis, where mitotic cyclins activate the CDKs .
6. CDKs possess two tyrosine phosphorylation sites: One causes activation of the enzyme; the other causes inactivation.
7. Specific kinases carry out both the stimulatory and the inhibitory phosphorylation
8. Similarly, protein phosphatases can remove phosphate from CDKs, either stimulating or inhibiting their activity, depending on the position of the phosphate.
9. The addition or removal of phosphate groups from CDKs is highly regulated and an important mechanism for the control of cell cycle progression .
10. Cyclin inhibitors play an important role in regulating the cell cycle in animals, and probably in plants as well, although little is known about plant cyclin inhibitors.
11. CDK activity can be regulated in various ways, but two of the most important mechanisms are (1) cyclin synthesis and destruction and (2) the phosphorylation and dephosphorylation of key amino acid residues within the CDK protein.

G2-M transition

1. A-type CDKs are expressed constitutively, while the plant-specific B-type CDKs increase expression during the G2-M transition point.
2. CDKA and CDKB subunits interact with their respective cyclin partners (CycA/B).
3. Both the expression of CDKA/B and CycA/B genes and the activity of CDKA/B kinases are affected by plant hormones.
4. Auxin, GA and cytokinin increase expression of these genes, and cytokinin can also induce removal of an inhibitory phosphate group (T14/Y15) on CDKA/B subunits.
5. In an additional level of control, phosphorylation at a separate site on CDKA/B subunits can induce activity of these subunits

Cell Cycle Checkpoint And Plant Growth Regulator

1. Cyclin A/B by Gibberellins.
2. D – type Cyclin by Cytokinin
3. Cdk inhibitor by Abscisic acid
4. Auxin also increases the expression of CDKA;1 and mitotic cyclins, although application of exogenous auxin alone is not sufficient to induce cell division.
5. Auxin and cytokinins are both necessary for progression through the G1-S and G2-M transitions as demonstrated in a variety of cultured plant cells.
6. Cytokinin can also increase the expression and kinase activity of CDKA;1 by a mechanism involving removal of an inhibitory phosphate group on the kinase.
7. In addition, CycD3;1 expression is also up-regulated by cytokinins.
8. CycD3;1 appears to be a critical regulator of G1-S progression