UNIT 11 Flashcards
“Cell cycle control”
Mitosis results in a dramatic re-organization of the entire cell. This is preceded by DNA replication, organelle replication and protein synthesis, all in preparation for cell division. The entire process is accomplished by a network of regulatory proteins known as
the cell cycle control system
By activating proteins responsible for carrying out each cell cycle- specific process at the appropriate time and by inactivating these proteins once the process is completed, the cell-cycle control system (2):
- ensures that each phase of the cell cycle is completed before the next one is begun
- ensures correct progression through each phase of the cell cycle.
The cell-cycle control system is based on
cyclically activated protein kinases
The cell-cycle control system is based on cyclically activated protein kinases. These kinases ___ multiple proteins involved in
DNA replication, mitosis and cytokinesis.
phosphorylate and activate
The effect of phosphorylation of cell-cycle protein machineries can be rapidly reversed by reactions carried out by another set of enzymes __
protein phosphatases
the concentration of the kinase __ change during the cell cycle
does not
the concentration of the kinase does not change during the cell cycle, it is
only activated at the appropriate time, after which it is rapidly inactivated.
the activity of each kinase
rises and falls in a cyclical fashion.
__ have to bind to the cell-cycle kinases before the kinases become enzymatically active.
Proteins called cyclins
Proteins called cyclins have to bind to the cell-cycle kinases before the kinases become enzymatically active. The cell-cycle kinases are therefore known as
cyclin-dependent protein kinases (Cdks).
Cyclins are so-called because
unlike the Cdks, their concentrations vary in a cyclical fashion during the cell cycle
concentration of cyclin throughout cell cycle?
concentration of cyclin varies in a cyclical fashion during the cell cycle
The effects of phosphorylation can be rapidly reversed by
protein phosphates
__ switch the cell-cycle kinase activity on and off, respectively
The periodic synthesis and degradation of cyclins
Even though there is cyclin B and Cdk present in other stages of the cell cycle (e.g. S and G2 phase), the complex between the cyclin and kinase is still subjected to:
further regulation by phosphorylation-dephosphorylation.
Cyclin B synthesis begins in
S phase
Cyclin B then accumulates and forms complexes with the __ throughout __ and __ phases.
Cyclin B then accumulates and forms complexes with the M phase Cdk throughout S and G2 phases.
Cyclin B then accumulates and forms complexes with the M phase Cdk throughout S and G2 phases. Although it associates with cyclin B, the M phase Cdk is active/inactive:
M phase Cdk is still enzymatically inactive.
At the end of interphase (in G2 phase), the M phase Cdk is activated by
a specific protein phosphatase called Cdc25 (activating phosphatase) that removes the inhibitory phosphate group, leaving the activating phosphates.
Once activated, the M phase Cdk phosphorylates and activates
a variety of target proteins that are required during mitosis in M phase. One target is
Cdc25, whose phosphorylation further activates the phosphatase activity, thus producing a positive feedback loop whereby activated cyclin B-M phase Cdk further activates itself.
Toward the end of mitosis, the M phase Cdk is inactivated by
proteolytic degradation of cyclin B. This inactivation of the M phase Cdk leads the cell to exit mitosis, undergo cytokinesis, and return to interphase (G1 phase).
Toward the end of G1 phase, the inactivated M phase Cdk is
dephosphorylated by a specific protein phosphatase. The inactive, unphosphorylated M phase Cdk kinase is now ready to form a complex with cyclin B.
Targets of cyclin B-M phase Cdk complex:
(1) chromatin condensation: phosphorylated protein targets: condensins
(2) mitotic spindle formation:phosphorylated protein targets: microtubule- associated proteins
(3) nuclear envelope breakdown:phosphorylated protein targets: lamins
During prophase
condensin becomes activated by cyclin B-M Cdk- mediated kinase activity. The protein then participates in chromatin condensation leading to the visible M-phase chromosomes.
The phosphorylation of microtubule-associated proteins during prophase promotes
their ability to cross- link the microtubules growing from opposite spindle pole poles, thereby leading to mitotic spindle formation.
