Lecture 14: Control of Cell Division

Control of cell division, apoptosis Major classes of the signal molecules that regulate cell size and cell numbers in an organ Mitogens: stimulate cell division by triggering G1-Cdk/S-Cdk Growth factors: stimulate cell growth (an increase in cell mass) Survival factors: suppress cell death (apoptosis) Growth factors mostly activate _______ • A. GPCR • B. RTK Checkpoints control cell cycle G1-Cdk —> favorable extracellular environment G1/S-Cdk —> DNA damage S-Cdk —> DNA damage M-Cdk —> unreplicated DNA, DNA damage APC/C —> chromosome unattached to spindle Which of the following is a cancer suppressor? • A. Myc • B. G1/S • C. Rb Which of the following is a gene regulatory protein? • A. P53 • B. P21 • C. G1/S Cdk Intracellular signal, which control the cell cycle, can arrest the cell cycle at the checkpoints Checkpoints generally operate through negative intracellular signals Signals emanate from incomplete jobs Only when the job is complete does the negative signal cease Three main checkpoints in the cell cycle Late G1 checkpoint: P53, mitogens, growth factors Late G2 checkpoint: cdc25 Metaphase checkpoint: through activation of cdc20/APC complex Which checkpoint mostly protects us from cancer? • A. Late G1 • B. Late G2 • C. Metaphase • D. All of the above Apoptosis Programmed cell death Suicide of the cell Billions of cells die in bone marrow every hour Half of the new neural cells die during development Neat death with recycling of cellular content: Cell shrinks The cell membrane shows irregular buds known as blebs Cytoskeleton collapses Nuclear envelope disassembles DNA breaks into fragments The cell breaks apart into several vesicles called apoptotic bodies, which are then phagocytosed Display signals that promote phagocytosis, such as phosphatidylserine, on their cell surface. Phosphatidylserine is normally found on the inner leaflet surface of the plasma membrane, but it is redistributed during apoptosis to the extracellular surface Mechanism of the cell destruction Procaspases are stored in the cell Procaspases can be activated by active caspases How are the first caspases activated? Procaspases have a very low proteolytic activity, insufficient to trigger caspases cascade Procaspases start to cleave each other when they are aggregated (induced proximity) Two possible ways to bring procaspases together: extrinsic and intrinsic Extrinsic Extracellular signal promotes aggregation of procaspases at the cell surface Intrinsic Release of the cytochrome C triggers the assembly of the apoptosome, which brings procaspases together Which of the following is activated by induced proximity ? • A. RTK • B. Procaspases • C. TGFbeta • D. All of the above