B1.2 What makes a cancer

Question 1

What are proto-oncogenes ?

Answer 1

Normal genes that code for proteins involved in progression of the cell cycle

Question 2

What do proto-oncogenes do ?

Answer 2

Increase proliferation

Anti-apoptosis

Question 3

What are oncogenes ?

Answer 3

Mutated versions of proto-oncogenes that code for protein products that stimulate growth and division.

They are over expressed meaning that they code for hyperactive proteins. This causes the cell to uncontrollably grow and divide

Question 4

What are tumour suppressors genes ?

Answer 4

Genes that have a negative regulation of the cell cycle. They codes fro proteins that stops cell cycle progression and promote apoptosis if there is DNA damage

Involved in DNA repair and inhibits transcription factors that push along the cell cycle

Question 5

What are the major players of tumor suppressor genes ?

Answer 5

p53

RB1

Question 6

What is the function of p53 ?

Answer 6

Blocks cell cycle in response to cellular damage, inducing apoptosis if DNA damage is irreparable

Question 7

Describe how p53 works .

Answer 7

1. Looks for DNA damage before cell enters the S PHASE
2. If DNA damage is detected, it binds to DNA and promotes transcription of gene p21 (activates genes that stop cell growth) or can even trigger cell death.
3. P21 binds and inhibits cycline and cycline dependant kinase 2 therefore preventing passage from G1 to S PHASE.
4. This buys time for DNA repair proteins to get to work
5. If DNA damage is irreparable, p53 induces apoptosis

Question 8

What is the function of RB1 ?

Answer 8

• Blocks cells cycle by binding and inhibiting E35 transcription factors
• Inhibits transcription of genes (cyclin-dependant kinase 2 gene) needed for cell cycle progression

Question 9

What inhibits the function of RB1 ?

Answer 9

Inhibited by phosphate (phosphorylation)

This leads to changes in gene expression

by stoping RB1 from activating cell proliferation by inactivating E2F

Question 10

What happens if there is a mutation in p53 ?

Answer 10

Cell can no longer repair DNA before S PHASE

Mutations build up

Leads to uncontrolled cell division

Question 11

What activates p53 ?

Answer 11

• Low oxygen concentration
• DNA damage
• Chemotherapeutic agents
• Other stresses

Question 12

What is the shape of p53 ?

Answer 12

Homotetramer

Question 13

What region of p53 binds to DNA ?

Answer 13

Central part

Question 14

How is the gene switched on by p53 ?

Answer 14

N-terminal transactional domain switches the gene on by recruiting RNA polymerase

Question 15

What is the function of E2 transcription factor ?

Answer 15

• Activates and binds genes for cell cycle progression
• Leads to gene expression
• Cell cycle can proceed

Question 16

When is RB1 active ?

Answer 16

When its unphosphorylated

Question 17

What does RB1 inhibit ?

Answer 17

E2F transcription factors

Question 18

What is the consequences of E2F being inhibited by RB1 ?

Answer 18

Cell cycle cant proceed bast G1 or S PHASE

Question 19

What are the major oncogenes ?

Answer 19

MYC and RAS

Question 20

How is cell proliferation achieved when MYC is activated ?

Answer 20

• Oncogenic stimulus is detected by the cell
• This produces more MYC proteins
• MYC will then target genes and regulate numerous pathways , positively and negatively
• This leads to cell proliferation

Question 21

What is RAS activated by ?

Answer 21

Growth factors

Question 22

What does RAS bind to and what are the consequences of these?

Answer 22

GDP (inactive)

GTP (active)

Question 23

What is RAS?

Answer 23

A G protein that is found on EGFR

Question 24

What pathway is activated when RAS is stimulated ?

Answer 24

1. RAS
2. RAD
3. MEK
4. ERK