15: Control of Cell Growth, Division, and Survival

What are extracellular signals

• signals from others cells for cells to survive, grow, and divide

• mostly soluble proteins that are secreted or bound to surface of other cells

What are examples of positive signals

1. Mitogens

2. Growth Factors

3. Signal Factors

What are mitogens?

• promotes cell division

• secreted signal proteins binds to cell-surface receptors

• release molecular ‘brakes’ that blocks progression to S phase and start transition (G1)

Examples of Mitogens?

PDGF and HGF

What does PDGF stand for? what is it

Platelet Derived Growth Factor

• released when blood clot forms

• binds to a receptor tyrosine kinase on undamaged cells

• cells activate to proliferate to heal the wound

What does HGF stand for? what is it?

Hepatocyte Growth Factor

• activates liver cells to proliferate if injured

What are Growth Factors?

1. stimulate cell growth (size and mass)

2. Promotes macromolecules synthesis

3. Inhbits macromolecules degradation

4.  does not depend on cell cycle control as the cell still grows after terminal differentiation (FINAL STAGE)

Whats an example of Growth Factors

PDGF stimulating cell growth and progression thru the cell cycle

• ensures cell maintains the right size when divdiing

What is apoptosis?

1. programmed cell death

2. regulates the number of animal cells

3. net and organized so it doesnt affect cellular neighbours

Example of apoptosis?

1. During development

• removes unneeded cells like webbing and tails of tadpoles to frogs

2. Adult tissues

• controls organ size like a piece of liver is removed then cells proliferate to replace the lost

What drug stimulates liver cell divison? what does apoptosis do?

Phenobarbital

• apoptosis brings the liver back to its normal size (WOAH, PAUSE, bring it back)

What are blebs?

irregular bulges on an apoptotic cell’s surface

How does apoptosis work?

1. Cell will start blebbing (cell will mutate and have humps coming off or lose its shape)

2. Shrink (losing water) and condense (pull stuff close tgt)

3. Cytoskeleton and nuclear envelope disassembles, and nuclear DNA break into fragments

What controls apoptosis? and define em

1. caspases - inactive proteases that receives a signal to activate apoptosis

2. intiator caspases - cleave and activate executioner caspases

3. executioner caspases - hunts key proteins keeping the cell alive and breaks them so nuclear envelope falls off and nucleus is now vulnerable

Example of what the executioner caspases targets?

• targets lamin proteins that make the nuclear lamina for nucleases to attack the nucleus

What are Bcl2 proteins? examples?

regulates caspase activity

• promotes or inhibits caspase activation and cell death

• Bax and Bak proteins activate when DNA is damaged

  • promote cell death

  • releases cytochrome c from mitochondria so no etc = no atp production

• Bcl2 prevents bax and bak releasing cytochrom c

  • inhibits apoptosis

What is cytochrome c activity?

• induces cell death by forming apoptosome

Whats apoptosome?

• large 7-armed, pinwheel-like protein complex

• recruits and activates initiator caspase

• triggers a caspase cascade

What is death receptor? example?

cell surface receptor that receives apoptotic signals from other cells

• death receptor Fas

How does Death receptor Fas work?

• activated by fas ligand (membrane bound protein)

  • on the surface of immune system cells called lymphocytes and natural killer cells

  • causing apoptosis in immune cells that arent needed/wanted

• triggers assembly of death-inducing signaling complex

  • includes initiator caspase w/c launches a caspase cascade

What are Survival Factors? example?

1. suppresses apoptosis and promote cell survival

2. extracellular signals ensure a cell only survives when and where its needed

• ex. nerve cells

  • has the same amount of survival cells and connecting cells

  • competition: if have enough survival cells then will live, if not then dies

What is Survival Factor deprivation?

if theres no survival factors to send then activation of caspase-dependent apoptosis occur

What are Inhibitory signals? example

• extracellular proteins that inhibit cell divison, growth, and survival

ex. myostatin

• inhibits growth and proliferation of myoblasts that fuse to form skeletal muscle cells during embryonic

• lack myostatin = muslce grow much larger than normal