important molecules

What is RAS? What happens to it when mutated?

• proto-oncogene involved in cell growth

• transmits signals from GF to nucleus

• gains a function of mutation and stays continuously active

• continuous proliferation and growth signals

what is MYC? What happens when mutated?

• proto oncogene

• transcription factor and regulated genes

• over expression/gene amplification

• increased transcription of GP promoting genes

What is p53? What happens when mutated?

• “guardian of genome”/tumor supressor gene

• regulates cell cycle arrest

• halts cell cycle in cases of dna damage or stress

• loss of function

• acumulation of genetic mutations

what is RB? what happens when mutated?

• tumor supressor gene

• “gatekeeper of the cell”

• regulates the cell cycle

• controls G1→ S by inhibiting E2F (e2f promotes growth into s phase)

• loss of function

• releases E2F which causes an uncontrolled progression from G1 to S

what is E2F? what happens when over active? What is it regulated by?

• A group of proteins that control how cells grow.

• Promotes cell development into S phase (when a cell duplicates its dna)

• regulated by RB
  
  

HPV mechanism

• E6 interferes with p53 (responsible for cell cycle arrest and apoptosis)

• E7 interferes with Rb, releasing E2F and encouraging entry into S phase

There are two pathways to senescence. What is the first one? (p53→p21)

• p53 → p21

1. stress activated p53

2. p53 stimulates p21

3. p21 inhibits CDK complexes

4. low levels of CDK allow for higher levels of Rb

5. Rb supressed E2F

6. cell remaines arrested

There are two pathways to senescence. What is the second one? (p16→Rb)

1. p16 inhibits CDK4/6

2. with CDK4/6 inhibited, RB remains active

3. Rb preents E2F from activating S phase

4. Cell cannot re-enter the cell cycle

What is BCL-2? What is in inhibited by?

BCL-2 is an anti-apoptotic protein inhibited by BH3-mimetic drugs

if a patient has high levels of BCL-2, what does this mean in terms of the cell?

BCL-2 is an anti-apoptotic. High levels of BCL-2 results in low levels of apoptosis

Describe the BH3-mimetic MOA

1. BH3-mimetic drug binds to BCL-2

2. BAK and BAX (pro-apoptotic proteins)

3. mitochondral membranes are permeable

4. cytochrome c is released

5. caspases are activated

6. apoptosis

what is the main function of BH3-mimetics

To inhibit the anti-apoptotic protein BCL-2

What are PARP proteins

a group of proteins that work on DNA repair in cells

What is PARPi’s function

PARP inhibitors inhibit the PARP repair proteins which ultimately results in cell death

There are two DNA repair pathways, What are they?

PARP proteins which work to repair single stranded DNA

BRCA1 and BRCA2 which repair double stranded DNA. (when both strands are repaired it is called homologous recombination)

What phase of interphase is revolved around growth and preperation

G1