1. Control of the Cell Cycle, Cell Signaling and Cancer Chapter 10 Section 9.3 & Chapter 5 Section 5.6 Biology In Focus AP Biology 2014 Ms. Eggers

2. Frequency of cell division varies

3. The cell cycle is controlled by molecular signals in the cytoplasm Fusing a cell in mitosis with a resting cell causes the resting G1 cell to enter that specific stage of mitosis Fusing a cell in mitosis with a resting cell causes the resting G1 cell to enter that specific stage of mitosis Conclusion? Conclusion?

4. Cell cycle control system = A cyclically operating set of molecules in the cell that both triggers and coordinates key events of the cell cycle = A cyclically operating set of molecules in the cell that both triggers and coordinates key events of the cell cycle A check point is a control point where stop and go signals regulate the cell cycle A check point is a control point where stop and go signals regulate the cell cycle

5. Checkpoints

6. Three main checkpoints to know: Damage to DNA and other external factors are evaluated at the G1 checkpoint; if conditions are inadequate, the cell will not be allowed to continue to the S phase of interphase. G1 checkpoint is a restriction checkpoint = a stop lightDNAinterphase The G2 checkpoint ensures all of the chromosomes have been replicated and that the replicated DNA is not damaged before cell enters mitosis.chromosomesmitosis The M checkpoint (also called the spindle checkpoint) determines whether all of the sister chromatids are correctly attached to the spindle microtubules before the cell enters the irreversible anaphase stage.chromatidsmicrotubules Source: Boundless. “Regulation at Internal Checkpoints.” Boundless Biology. Boundless, 14 Nov. 2014. Retrieved 18 Nov. 2014 from https://www.boundless.com/biology/textbooks/boundless-biology-textbook/cell- reproduction-10/control-of-the-cell-cycle-89/regulation-at-internal-checkpoints-398-11625/

7. Checkpoint signal molecules Regulatory proteins & protein complexes: Regulatory proteins & protein complexes: Kinases: enzymes that regulate other proteins by phosphorylating them (adding a phosphate can activate or inactivate) Kinases: enzymes that regulate other proteins by phosphorylating them (adding a phosphate can activate or inactivate) Cyclins: proteins that control progression through the cell cycle by activating cyclin- dependent kinases Cyclins: proteins that control progression through the cell cycle by activating cyclin- dependent kinases

8. Levels of cyclins during cell cycle stages

9. Cyclins activate CDKs which activate other proteins

10. Maturation-promoting factor (abbreviated MPF) Maturation-promoting factor (abbreviated MPF, also called mitosis-promoting factor or M-Phase- promoting factor) is a protein composed of cyclin B and cyclin- dependent kinase (CDK1) that stimulates both mitosis and meiosis. Maturation-promoting factor (abbreviated MPF, also called mitosis-promoting factor or M-Phase- promoting factor) is a protein composed of cyclin B and cyclin- dependent kinase (CDK1) that stimulates both mitosis and meiosis. MPF promotes the entrance into mitosis (the M phase) from the G2 phase by phosphorylating multiple proteins needed during mitosis. MPF promotes the entrance into mitosis (the M phase) from the G2 phase by phosphorylating multiple proteins needed during mitosis.

11. Let’s back up and talk about cell signaling…

13. Signal molecule = message The chemical messenger sent out by one cell that elicits a response in another cell. Can be large such as a protein growth factor, a steroid hormone such as estrogen, a small neurotransmitter such as acetylcholine which stimulates muscles to contract, and even something as small as the gas nitric oxide (NO). The chemical messenger sent out by one cell that elicits a response in another cell. Can be large such as a protein growth factor, a steroid hormone such as estrogen, a small neurotransmitter such as acetylcholine which stimulates muscles to contract, and even something as small as the gas nitric oxide (NO).

14. Receptor = receiving end The signaling molecule is a ligand, which is a molecule that binds to and interacts specifically with another molecule. The signaling molecule is a ligand, which is a molecule that binds to and interacts specifically with another molecule. The molecule to which a signaling ligand binds is called a receptor. The molecule to which a signaling ligand binds is called a receptor. Receptors can be integral membrane proteins OR located within the cytoplasm Receptors can be integral membrane proteins OR located within the cytoplasm Only cells with the ligand-specific receptor will respond to the signal = VERY SPECIFIC Only cells with the ligand-specific receptor will respond to the signal = VERY SPECIFIC

15. How does a cell ‘hear’ a message? The signal transduction pathway Signal  Receptor  Relay molecules  Activation

16. Where can receptors be located?

17. How might a target cell respond? Ligand might open a protein channel in the membrane directly by changing the conformation (shape) of the receptor – ion channel receptors Ligand might open a protein channel in the membrane directly by changing the conformation (shape) of the receptor – ion channel receptors Ligand might bind to a receptor in the cytoplasm that then travels to the nucleus and changes gene expression – steroid hormone receptors Ligand might bind to a receptor in the cytoplasm that then travels to the nucleus and changes gene expression – steroid hormone receptors Ligand might activate a secondary messenger such as a kinase (an enzyme that phosphorylates another protein, thereby changing its activity) -- G protein-coupled receptors, receptor tyrosine kinases, etc. Ligand might activate a secondary messenger such as a kinase (an enzyme that phosphorylates another protein, thereby changing its activity) -- G protein-coupled receptors, receptor tyrosine kinases, etc.

18. Ion channel receptors

19. Steroid hormone receptors

20. G-protein coupled receptors

21. G protein coupled receptor & cAMP second messenger: AMPLIFICATION

22. Cell signaling can (and often does) result in changes in gene expression in the target cell

23. A growth factor is a protein released by certain cells that stimulates other cells to divide.

24. A VERY common method for activating and inactivating important proteins is by phosphorylating them A kinase is an enzyme that adds a phosphate group to another protein.

25. Now, back to the cell cycle. Message from outside the cell can activate a signal transduction pathway that turns on the genes that make cyclins. The cyclin proteins made from these genes can then turn on the cell cycle & cells begin to divide…

26. Wound  Responding cells send out signal molecules that tell nearby cells to start dividing for tissue repair. Cell cycle is activated.

27. Cancer = unregulated cell division  happens when cells divide out of control

28. Just as there are signals to tell cells to divide, there are also signals that tell cells to NOT divide Density-dependent inhibition: a phenomenon in which crowded cells stop dividing Density-dependent inhibition: a phenomenon in which crowded cells stop dividing Adjoining cells send a cell division-inhibiting signal to their neighbors Adjoining cells send a cell division-inhibiting signal to their neighbors Anchorage dependence: Most cells must be attached to a substratum (some sort of surface or extracellular matrix) in order to divide Anchorage dependence: Most cells must be attached to a substratum (some sort of surface or extracellular matrix) in order to divide

29. Cancer cells do not show density-dependent inhibition, anchorage dependence and don’t require growth factors

30. Cancer vocabulary Transformation: the term for when a normal body cell mutates to become a cancer cell Transformation: the term for when a normal body cell mutates to become a cancer cell A benign tumor is composed to abnormal cells that proliferate but do not have the capacity to spread and invade other tissues A benign tumor is composed to abnormal cells that proliferate but do not have the capacity to spread and invade other tissues A malignant tumor is made up of cancer cells that proliferate out of control and can spread to new tissues (called metastasis). Cancer is the disease caused by malignant tumors. A malignant tumor is made up of cancer cells that proliferate out of control and can spread to new tissues (called metastasis). Cancer is the disease caused by malignant tumors.

31. Question Lectins are naturally occurring plant proteins that help promote increased mitosis within plant root tips. These proteins influence the normal production of MPF within the root cells and thereby speed up the cell cycle. In no more than three sentences, state ONE similarity and TWO differences between Lectin influenced cells and cancer cells. Lectins are naturally occurring plant proteins that help promote increased mitosis within plant root tips. These proteins influence the normal production of MPF within the root cells and thereby speed up the cell cycle. In no more than three sentences, state ONE similarity and TWO differences between Lectin influenced cells and cancer cells.

32. Cancer and the cell cycle animated tutorials Cancer and the cell cycle animated tutorials Cancer and the cell cycle animated tutorials Cancer and the cell cycle animated tutorials