Cell Cycle and Cancer (Lecture 3) Flashcards
Regulation of the Cell Cycle
Why can’t cell division occur all the time?
Cell division cannot occur all the time because uncontrolled division is dangerous and can lead to cancer
Regulation of the Cell Cycle
How is the progression through the cell cycle controlled?
Progression through the cell cycle is controlled by proteins that appear and disappear in a cyclical fashion, and by several enzymes that become active and inactive, also in cycles
Regulation of the Cell Cycle
What are the proteins that appear and disappear cyclically called?
The proteins that appear and disappear cyclically are called cyclins.
Transitions in the cell cycle need to be regulated
When do these regulators need to function?
These regulators need to function at specific times
Transitions in the cell cycle need to be regulated
How is the function of an enzyme controlled?
1) Presence or absence
2) Modification such as phosphorylation
3) Turnover or half-life
4) Co-regulators
Regulation of the cell cycle
What do cyclins bind to and activate?
Cyclins bind to and activate cyclin-dependent kinases (CDK) to control progression through the cell cycle
Regulation of the cell cycle
What do Cyclin-CDK complexes phosphorylate?
Cyclin-CDK complexes phosphorylate target proteins that promote cell division.
Progression through the cell cycle
Explain what happens to the level of protein as the embryo divides by mitosis
Level of protein increases and decreases, and then increases and decreases again as the embryo divides by mitosis
Cyclin-CDK Complexes
What does the M-cyclin CDK help with?
M cyclin–CDK helps prepare the cell for mitosis.
S cyclin– CDK helps initiate DNA synthesis.Cyclin-CDK Complexes
What does the S-cyclin CDK help with?
S cyclin– CDK helps initiate DNA synthesis.
Cyclin-CDK Complexes
What does the G1/S cyclin-CDK complex do?
G1/S cyclin–CDK complex prepares cell for DNA replication
Cell Cycle Checkpoints
What is a cell cycle checkpoint?
Cells have many cell-cycle checkpoints, where they can pause the cell cycle if something is not right, before progressing to the next stage
Cell Cycle Checkpoints
What are the three checkpoints?
- DNA replication
- DNA damage checkpoint
- Spindle assembly checkpoint
Cell Cycle Checkpoints
What is the DNA replication checkpoint?
DNA replication checkpoint: Checks for the presence of unreplicated DNA at the end of G2 before the cell enters mitosis
Cell Cycle Checkpoints
What is the DNA damage checkpoint (brief)?
DNA damage checkpoint: checks for damaged DNA before the cell enters S phase
Cell Cycle Checkpoints
What is the spindle assembly checkpoint?
Spindle assembly checkpoint (before anaphase): checks for all chromosomes being attached to the spindle before the cell progresses with mitosis
Explain the DNA damage checkpoint in detail
- Genes that inhibit the cell cycle are OFF
- p53 is a protein found in the nucleus.
- DNA damage activates protein kinases that phosphorylate p53
- Phosphorylated p53 acts as a transcription factor that turns on genes that inhibit the cell cycle
- Inhibiting the cell cycle gives the cell time to repair the damaged DNA
Transitions in the cell cycle need to be regulated
With the addition of CDK inhibitor (information slide)
Multiple Mutation Model for Cancer Development
In normal cells?
Inactivation of first tumor suppressor gene
Multiple Mutation Model for Cancer Development
In Benign cancer cells?
Activation of oncogene
Multiple Mutation Model for Cancer Development
In Malignant cancer cells?
Inactivation of second tumor suppressor gene
Multiple Mutation Model for Cancer Development
In Metastatic cancer cells?
Inactivation of third tumor suppressor gene or activation of second oncogene
In colon, stem cells proliferate…
Slowly proliferating (~1X every 2 days)
In colon, transit-amplifying cells proliferate…
Fast (~1X every couple of hours)
Colon Cancer
What often leads to cancer?
Multiple mutations in tumor suppressors or proto-oncogenes in different signaling pathways that control the cell cycle often leads to cancer
