Lecture 15: Cell Cycle Control System Flashcards
The cell-cycle protein machineries include:
protein machinery involved in DNA replication and in mitosis and cytokinesis.
The cell-cycle control system switches the cell-cycle protein machineries_______ at the correct times.
on and off.
Which protein kinase is the cell-cycle control based on
cyclically activated protein kinases.
Define cyclically activated protein kinases
They phosphorylate and activate proteins involved in DNA replication, mitosis/cytokinesis and activated only at appropriate times (quickly inactivated). They’re activity rises and falls in a cyclical fashion.
The effect of phosphorylation of cell-cycle protein machineries can be rapidly reversed by reaction carried out by anther set of enzymes called
protein phosphatases (removal of phosphate).
How is the kinase activity of cyclically activated protein kinases switched on and off at the appropriate time?
cyclins have to bind to cell-cycle kinases before they become enzymatically active. Cyclins concentration vary in a cyclical fashion during the cell cycle. Their synthesis and degradation switch cell-cycle kinase activity on and off.
What’s another name for cyclically activated protein kinases?
cyclin-dependent protein kinases (Cdks).
Define MPF
M-phase Promoting Factor is the cyclin-Cdk complex that controls protein entry to M phase, then M phase Cdk phosphorylates and activates proteins required during M phase.
Steps in mechanism of MPF regulation
Step 1:
- cyclin B synthesis begins in S phase, which accumulates and forms complexes with M phase Cdk throughout S and G2 phases. M phase Cdk enzymatically inactive.
Step 2: As complexes form the M phase Cdk is phosphorylated by an activating kinase (site for activity) and inactivating kinase (over-riding site that inhibits activity). M phase Cdk enzymatically inactive.
Step 3: at the end of interphase (G2 phase) M phase Cdk is activated by an activating protein phosphatase that removes the inhibitory phosphate group. Once activated it phosphorylates proteins required during M phase.
Step 4: at the end of mitosis, M phase Cdk is inactivated by proteolytic degradation of cyclin B, which leads the cell to exit mitosis, undergo cytokinesis, and return to interphase.
Step 5: at the end of G1 phase inactivated M phase Cdk is dephosphorylated by a specific protein phosphatase, inactive form of M phase Cdk is ready to form complex with cyclin B.
MPF targets which processes and what proteins associated with it
1) chromatin condensation: condensins, replicated chromosomes condense and now visible.
2) mitotic spindle formation: microtubule associated proteins, such as the ones that cross link polar microtubules.
3) nuclear envelop breakdown: lamins are phosphorylated causing the nuclear envelope to disassemble into small membrane vesicles.
By phosphorylating and activating key target proteins required during mitosis, MPF induces multiple
nuclear and cytoplasmic changes which reorganize the structure of the cell during M phase.
Different cyclin –Cdk complexes trigger which steps in the cell cycle?
(1) “cyclin E–G1 phase Cdk” : G1 to S transition.
(2) “cyclin A–S phase Cdk” : progression of cells through S phase.
(3) “cyclin B–M phase Cdk” : transition from G2 to M phase.
