Lecture 4

Question 1

How does a retrovirus integrate its RNA into our DNA?

Answer 1

Via reverse transcriptase the RNA is translated into DNA, which then can integrate to the host genome

Question 2

Which virus mutated gene creates cancer?

Answer 2

V-Src

Question 3

What are genetic changes and altered gene expression called?

Answer 3

A changed molecular landscape of cancer

Question 4

What do ‘p’, ‘c’ and ‘g’ stand for in the notation of mutations?

Answer 4

P = protein
C = complementary DNA
G = genomic DNA

Question 5

What changes can be made in the RNA level to change protein levels?

Answer 5

Produce more, degrade less, differential splicing

Question 6

What changes an be made on the protein level to change protein levels?

Answer 6

Production, modification, degradation and translocation

Question 7

How does protein phosphorylation take place?

Answer 7

Kinases do this to amino acids with a free OH

Question 8

Which three amino acids have a free OH?

Answer 8

Tyrosine, serine and threonine

Question 9

Which three phosphorylation kinases are there?

Answer 9

Thyrosine kinases, serine/threonine kinases and dual kinases

Question 10

Which three protein phosphatoses are there?

Answer 10

Thyrosine, serine/threonine and dual

Question 11

How do kinases work?

Answer 11

An ATP put a P on the free OH.

Question 12

How can kinases be inhibited?

Answer 12

Can be inhibited by having something bind to the ATP site (kinase inhibitor, KI)

Question 13

What is phospho-tyrosin recognised by?

Answer 13

The SH2 domain

Question 14

What does the process of GTP binding to Ras-like GTPases look like?

Answer 14

When Ras is bound to GDP it is inactive, to then it is bound to GTP via GEFs and GAP transforms GTP back to GDP

Question 15

Through what type of receptors do steroid hormones work?

Answer 15

Through nuclear receptors

Question 16

How can EGFR signaling be done?

Answer 16

It can be done via dimerization of the receptor and then autophosphorylation or via phosphorylation of the receptor as normal

Question 17

What is the process of EGFR signaling?

Answer 17

SH2 recognises the phospho-tyrosine and binds, Grb2 binds, GEF binds with Ras and Raf, which phosphorylates MEK -> ERK -> MADK, which then goes to the nucleus to phosphorylate transcription factor

Question 18

What is different with ErBB1 and HER1 compared to EGFR signaling?

Answer 18

They are similar, but have multiple receptors and ligands, as well as different downstream effect

Question 19

How many effectors and ligands can be found in ErBB1?

Answer 19

4 receptors and multiple ligands

Question 20

What does a photon receptor sense and how does it work?

Answer 20

It senses light and it has a beta-gamma domain and an alpha domain, the alpha comes loose when GTP is bound

Question 21

How does an adhesion receptor work?

Answer 21

Integrin binds to FAK then to Ras and to MAP kinase

Question 22

What is an activating mutation?

Answer 22

A missense mutation

Question 23

What is an inactivating mutation?

Answer 23

A nonsense mutation

Question 24

What does the missense mutation V600E cause?

Answer 24

BRAF activation

Question 25

What is the RET oncogene important for and what can it cause?

Answer 25

It is important in neural development and it causes hereditary tumor syndromes

Question 26

How many phosphorylation sites do RET oncogenes have?

Answer 26

Many of them, but all are tyrosine (y)

Question 27

Which mutation can be found in RET oncogenes?

Answer 27

MEN2A/ FMTC/ MEN2B, they all fit specific syndromes

Question 28

Which missense mutations can be found in RAS and what is their consequence?

Answer 28

A mutation 12, 13, 61. They inhibit GTP to GDP conversion

Question 29

What can a BCR-ABI translocation induce?

Answer 29

Adhesion, apoptosis, transformation, proliferation, differentiation

Question 30

What does oncogene addiction mean?

Answer 30

The oncogene is dependent on a pathway, so if you inhibit it you will kill the cell

Question 31

What is an example of using oncogene addiction to your benefit in the clinic?

Answer 31

EGFR-Ras mutation in lung cancer, can kill the cells with the inhibitor Gefitnib

Question 32

Which mutation can be found in melanoma and how can you inhibit it?

Answer 32

V600E BREF mutation, this can be inhibited with TKI Vemurafenib

Question 33

What is controversial about the BREF inhibitor?

Answer 33

It can also cause cancer (it comes back)