Cell Cycle Regulation

1. Cell Cycle Regulation

2.  A. The cell-cycle control system triggers the major processes of the cell cycle  B. The control system can arrest the cell cycle at specific checkpoints  C. The cell cycle control system is based on cyclically actived protein kinases---cyclin-dependentkinases (Cdks).

3. Checkpoints

4. Checkpoints • A checkpoint in the cell cycle is a critical control point where stop and go signals regulate the cycle. • Three major checkpoints are found in the G1, G2, and M phases.

5. G1checkpoint • The most important check for mammalian cells • a go-ahead signal, allows completion of the cell cycle and divides. • No go-ahead signal, the cell exits the cycle and switches to a non-dividing state, the G0 phase. • Most human cells are in this phase. • Liver cells can be “called back” to the cell cycle by external cues (growth factors), but highly specialized nerve and muscle cells cannot

6. Fluctuations • Rhythmic fluctuations • control molecules pace the cell cycle • protein kinase • Levels present in constant amounts • require a second protein, a cyclin, to become activated • levels of cyclin proteins fluctuate cyclically • The complex of kinases and cyclin forms cyclin- dependent kinases (Cdks)

7. MPF – maturation promoting factor • MPF promotes mitosis • Triggers passage past the G2 checkpoint to the M phase. • stimulates fragmentation of the nuclear envelope

8. M phase checkpoint • chromosomes are attached to the spindle at the metaphase plate. • Ensures daughter cells do not end up with missing or extra chromosomes. • Kinetochores that have not attached to spindle microtubules signal to delay anaphase.

9. Anaphase promoting complex APC • When all kinetochores are attached, the APC activates, triggering breakdown of cyclin and inactivation of proteins uniting sister chromatids together.

10. External factors • Growth factors • Cells are stimulated to grow • Anchorage dependence factors • Cells must be anchored to matrix of tissues before division can occur • Cancer cells do not have this factor • Density-dependent factors • At high densities, cells are inhibited from growing • Cancer cells do not have this factor

11. Cancer • Cells divide excessively and invade other tissues • Cells do not stop dividing when growth factors are depleted because they; • manufacture their own • have an abnormality in the signaling pathway, or • have a problem in the cell cycle control system

12. Abnormal behaviour of cancer cells • Begins when a single cell in a tissue undergoes a transformation that converts it from a normal cell to a cancer cell • Have chromosomal and metabolic abnormalities • Normally, the immune system recognizes and destroys transformed cells. • However, cells are not destroyed proliferate to form a tumor - a mass of abnormal cells. • If the abnormal cells remain at the originating site, the lump is called a benign tumor. • Most do not cause serious problems and can be removed by surgery.

13. Malignant tumor • Cancer cells leave the original site and can invade and impair the functions of one or more organs. • cancer cells often lose attachment to nearby cells, are carried by the blood and lymph system to other tissues, and start more tumors in a event called metastasis.

14. Task • Read the E-bio assignment Cancer and Mitosis. Answer questions at end of article.