p53

Question 1

What are the 4 main functions of p53?

Answer 1

Tumour suppressor
Guardian of the genome
Mutant p53 can act as oncogene
Transcription factor

Question 2

Around what year was p53 discovered?

Answer 2

1979

Question 3

p53 was originally identified by interaction with what?

Answer 3

Viral proteins:
Large T antigen of SV40
E1B of adenovirus
E6 of papillomavirus

Question 4

What was p53 first thought to be?

Answer 4

An oncogene

Question 5

What does p53 suppress?

Answer 5

Cell transformation

Question 6

What is mutated in a high proportion of human cancers?

Answer 6

p53

Question 7

What is Li-Fraumeni syndrome?

Answer 7

A rare, dominant-inherited cancer syndrome where patients have a germline mutation in the TP53 gene

Question 8

p53 protects against cancer, true or false?

Answer 8

True

Question 9

What type of protein is p53?

Answer 9

A nuclear phosphoprotein

It is a transcription factor

Question 10

What form does p53 act in?

Answer 10

Its tetrameric form

Question 11

What does p53 recognise in promoters?

Answer 11

A 10bp consensus sequence:

5’- Pu.Pu.Pu.C.A/T.A/T.G.Py.Py.Py -3’

Question 12

What exons in p53 are mutations clustered?

Answer 12

In exons 5-8 (10 exons)

Question 13

What amino acids in p53 are hotspots for mutations?

Answer 13

Amino acids 175, 248 and 273

Question 14

What do mutant versions of the p53 protein interfere with?

Answer 14

Normal p53 function

Question 15

When is p53 expressed at very low levels?

Answer 15

In the absence of damage

Question 16

What is the half life of p53?

Answer 16

20 minutes

Question 17

What is the main role of p53?

Answer 17

To define the cellular responses to different kinds of damage, but it has many other functions, both in response to stress and normal conditions

Question 18

Some p53 functions can even be what?

Answer 18

Antagonistic (and simultaneous)

Question 19

Do functions of p53 require the transcription of genes (transactivation)?

Answer 19

Some do and some do not

Question 20

Where are the functions of p53 performed?

Answer 20

Some in the nucleus, some in the cytosol

Question 21

How is p53 activated?

Answer 21

Through post-translational modifications

Question 22

In terms of the p53 pro-survival function, what are basal levels of p53 regarded as?

Answer 22

Antioxidant

Question 23

Describe the metabolism of normal cells

Answer 23

Oxidative phosphorylation of pyruvate in mitochondria

Question 24

Describe the Warburg effect

Answer 24

Cancer cells mostly use aerobic glycolysis to obtain energy, instead of oxphos

Question 25

What tumour suppressor gene is probably the most studied and most important?

Answer 25

p53

Question 26

Why was p53 first thought to be an oncogene?

Answer 26

Because the protein detected was a mutant form

Question 27

Is a mutation in p53 sufficient enough to cause cancer?

Answer 27

No, need some sort of inactivation of downstream pathway to become cancerous

Question 28

What region of p53 is where a lot of viral proteins can bind?

Answer 28

SV40 T antigen binding

Question 29

Which exons of p53 bind to DNA

Answer 29

Exons 5-8

Question 30

Where do most of the phosphorylations of p53 occur?

Answer 30

At the start

Question 31

Most activators of p53 are kinases, true or false?

Answer 31

True

Question 32

What happens if p53 is activated outside the nucleus?

Answer 32

It can move to the mitochondria and help release things from the mitochondria for apoptosis for example

Question 33

Can pro-survival work during apoptosis?

Answer 33

Yes