Regulation of the Cell Cycle

1. Regulation of the Cell Cycle

2. Internal and External Factors • Cell cycle is known, so now we ask what controls it • We have observed many factors that influence a cell’s ability to move forward in the cycle • Kinetochores not attached to microtubules • Density dependent inhibition • Anchorage dependence

3. Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). 25 µm Normal mammalian cells

4. Molecular Control • The question becomes, what is happening in the cell • Experiments have shown that proteins are the control molecules

5. The Rao Johnson Experiment Experiment 1 Experiment 2 M S G1 G1 M S M S When a cell in the M phase was fused with a cell in G1, the G1 cell immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. Something in M phase induced interphase cells to divide. When a cell in the S phase was fused with a cell in G1, the G1 cell immediately entered the S phase—DNA was synthesized. S cells contained something that induced regulation in G1 cells.

6. Conclusion: the S phase proteins work on G1 nuclei, M phase works on everything • Biologists determined it was a complex of two proteins called mitotic promoting factor (MPF) • Made of cyclin dependent kinase (CDK) and cyclin • Kinase enzymes turn other proteins on and off by phosphorylating them inactive cycle protein  ------------->active-PATP ADP

7. MPF phosphorylates key proteins, inducing mitosis • And, activates a protein that destroys cyclin • So, it shuts off further division when it has been activated • Similar all three portions of interphase • Each is referred to as a “checkpoint” • Collectively, they are called growth factors • The cell has mechanisms that ensure each phase is complete before moving onto the next • We have seen this already with the possibility of a cell entering G0

8. LE 12-15 G0 G1 checkpoint G1 G1 If a cell does not receive a go-ahead signal at the G1 checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state. If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

9. Cancer • Cancer can be thought of as uncontrolled growth of cells • They may lack the mechanisms, do not respond properly to them, or have an error in the pathways • If they stop, it is at a random point

10. Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. 25 µm Cancer cells

11. A mass of cancer cells is known as a tumor • If this tumor stays in the original site – benign • If it spreads to surrounding tissue - malignant • A individual tumor cell can break free from the group and invade other organs • It is said to have metastasized • Metastasis http://www.youtube.com/watch?v=rrMq8uA_6iA&feature=related • Unfortunately, these cells can continue to grow if supplied with nutrients • Normal cells divide 25-50 before dying

12. Telomeres • A hexanucleotide sequence TTAGGG • Holds DNA together • A portion of this is lost every time a cell divides • When it is lost, DNA unwinds, cell death • Cancer cells have telomerase • Continually rebuilds the telomeres • They are “ageless”

13. Cancer Lymph vessel Tumor Blood vessel Glandular tissue Metastatic tumor Cancer cell A small percentage of cancer cells may survive and establish a new tumor in another part of the body. Cancer cells invade neighboring tissue. A tumor grows from a single cancer cell. Cancer cells spread through lymph and blood vessels to other parts of the body.

14. Treatments • The two most common treatments we have are chemotherapy and radiation treatments Chemotherapy • By definition, treatment of any condition via chemicals • Our focus is on antineoplastic drugs – cancer fighters • Act by targeting rapidly dividing cells • However, this also includes healthy cells such as bone marrow (blood cells) and hair follicles, and sex cells

15. Common side effects – hair loss and a compromised immune system • Essentially theory is the drugs will kill the cancer faster than the patient • If not discovered soon enough, treatment would take too long Radiation Therapy • Beam of subatomic particles that damages DNA • Has to focus on a tumor

16. Alternatives • With more knowledge on mechanisms of cancer, new treatments are being proposed • Viruses are being designed to specifically target cancer cells