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Unformatted text preview: BIO 106 Fall 2009 Professor Owen 11/5/2009 Regulation Regulation of the Cell Cycle
Cell division is very tightly regulated. Why? How? What controls the progression of steps past checkpoints?
ECB3 18-3 Evans et al. (1983) Cyclin: A protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33: 389-396. Regulators Regulators of Cell Cycle Progression:
Cooper 16.12 CyclinCyclin-dependent Kinases Studies of proteins synthesized during the cell cycle showed sea urchin embryos accumulate then rapidly degrade the protein called cyclin. Cyclin dependent kinases (Cdk) control cell division. Mitotic-Cdk activity peaks at mitosis. What is a Cdk? ECB3 18-8 CyclinCyclin-dependent Kinases
What is the function of a protein kinase? A. Convert ATP to cAMP B. Convert ADP to ATP C. Take phosphate from ATP and put on target protein D. Take phosphate from GTP and put on target protein Mitotic-Cdk activity corresponds to a peak in concentration of mitotic-cyclin. ECB3 18-5 Cells-25 Cell Cycle-Apoptosis 1 BIO 106 Fall 2009 Professor Owen 11/5/2009 Cdk
A cyclin-dependent cyclinkinase (Cdk) needs a cyclin to be enzymatically active, phosphorylating target proteins. Its kinase activity is cyclincyclin-dependent.
ECB3 18-4 Activation of Cdk Activation of Cdk requires it be phosphorylated, then partially dephosphorylated. dephosphorylated.
ECB3 18-9 Control of Cdk?
In what way would you predict the cell controls its activity of Cdk?
What ways could you imagine to control the activity of a Cdk? HINT: What ways does a cell control its levels of a protein? A. Remove the mRNA for Cdk Remove B. Remove the Cdk protein by polyubiquination C. Remove the cyclin protein by polyubiquination
The cell degrades the cyclin protein by the process of polyubinitination. polyubinitination.
2004 Nobel Prize in Chemistry – function of ubiquitin
ECB3 10-11 CyclinCyclin-dependent Kinases Distinct Cdks Trigger Different Phases of the Cell Cycle Cyclin dependent kinases (Cdk) control cell division. The loss of cyclin turns off ECB2 18-6 the Cdk. ECB3 18-10 Cells-25 Cell Cycle-Apoptosis 2 BIO 106 Fall 2009 Professor Owen 11/5/2009 The G1 Checkpoint G0 What is a logical necessity for the G0 path of the cell cycle? A. Stop the cell cycle if the DNA is irreversibly damaged B. Stop the cell cycle if the cell lacks Stop the cell cycle if the cell lacks nutrients nutrients C. Stop the cell cycle if the organism is dead D. Stop the cell cycle if the moon phase is wrong The G1 checkpoint is a crossroad. The cell can commit to completing another cell cycle, or pause, or stop (G0).
ECB3 18-12 Cell Cell Cycle Checkpoints What Controls the G1 Checkpoint?
The transcription factor protein p53 plays major role in checking the plays a major role in checking the integrity integrity of the DNA before continuing the cell cycle. p53 is a tumor suppressor gene. gene. The cell-cycle control system can arrest the cycle at cellvarious checkpoints – can apply molecular brakes. ECB3 18-13 Action of p53 DNA DNA Damage Stops the Cell Cycle
When DNA is damaged, the p53 protein, which is normally rapidly degraded, becomes stabilized and active. This leads to inactivation of the cell cycle by activating p21. Cooper 18.38 ECB3 18-16 Cells-25 Cell Cycle-Apoptosis 3 BIO 106 Fall 2009 Professor Owen 11/5/2009 Cell Activity is Controlled by Signals
Note that external signals regulate cell division cell division, differentiation, and life. The lack of signals leads to cell death (apoptosis). apoptosis). Apoptosis Apoptosis is an important normal destiny of some cells during development, as seen here in a developing mouse paw (bright green dots). No webbed fingers one day later!
ECB2 16-6 ECB3 18-36 ECB3 18-37 Apoptosis
Apoptosis helps eliminate the tail during the metamorphosis of a tadpole into a frog. What is another example of when apoptosis could occur? A. Removal of a damaged limb B. Removal of a cell with Removal of cell with damaged damaged DNA Maize roots –if the soil is water-logged can watercreate air spaces by apoptosis. Apoptosis Apoptosis kills cells quickly and cleanly. Damaged cells die in a messy way.
modified from ECB3 18-38 Cells-25 Cell Cycle-Apoptosis 4 ...
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