Biochemistry - Tumour Suppressor Genes

Question 1

Tumour Supressor Genes

Answer 1

These are genes regulating cell growth, preventing tumour formation and genomic stability maintenance

Question 2

What may TSG regulate?

Answer 2

Cell cycle progression, DNA repair, apoptosis and cell adhesion

Question 3

What is an example of TSG?

Answer 3

TP53 formation of P53 protin

Question 4

P53

Answer 4

This is a TF regulating clel cycle arrest gene expresison, halting G1/S checkpoint when actvie

Question 5

Why does cancenr development require mutaitons of both alleles?

Answer 5

TSG are recessive

Question 6

Retinoblastoma Protein

Answer 6

This is a critical TSG blocking cell cycle progression by inhibition of E2F TF

Question 7

What are examples of TSG??

Answer 7

Retinoblastoma Protein
P53

Question 8

What is the occurence of RB?

Answer 8

10% in eyes of young children whilst 90% later in life

Question 9

What is E2F importan in?

Answer 9

DNA replication and cell cycle progression

Question 10

What is the mechanism of RB?

Answer 10

Active in hyper-phosphorylated state, binding E2F TF to prevent transcription, phosphorylated by CDK

Question 11

Somatic

Answer 11

Occuring throuhgout ones life

Question 12

What is RB caused by in tumorgenesis?

Answer 12

Somatic and Germline(Inherited)

Question 13

Loss of Heteroxygosity

Answer 13

This is where diploid cells heteroxygous for a mutant allele lose their wild type allel through mutations

Question 14

How may LOH result?

Answer 14

Duplication of the mutant RB1 allele and loss of wild type, thus no RB1 disrupts apoptosis

Question 15

What happens when RB is lost?

Answer 15

G1 checkpoint lost and cell division no longer requires mitogen stimulation

Question 16

P53

Answer 16

This is a TF activating many genes involved in essential maintenace of genetic stability.

Question 17

What does P53 do?

Answer 17

Arrest cell cycle allowing DNA repair machinery more time to fix DNA before pmitosis

Question 18

How is P53 expressed?

Answer 18

Constantly expressed and constantly degraded in absence of genetic damage

Question 19

How is P53 activated?

Answer 19

Stressors in the cell activate upstream signalling pathways wiht P53 translocation into nucleus and bind to response elements involves in cell processes

Question 20

What is P53 constant degradation prevented by?

Answer 20

Phosphorylation and stabilization

Question 21

What pathways does P53 regulate?

Answer 21

DNA repair, cell cycle arrest and apoptosis

Question 22

P21

Answer 22

This is an inhibitor of cyclin-dependent kinase, upregulated by P51

Question 23

What does P21 do?

Answer 23

Inhibit Cyclin E-CDK2 complex, preventing G1 exit

Question 24

PUMA(P53 Upregulated Modulator of Apoptosis)

Answer 24

This is a critical mediator of P53 dependent and P53 independent kinase

Question 25

How does P53 regulate apoptosis?

Answer 25

Aactivaiton of pro-apoptoic genes like PUMA

Question 26

What is the process of apoptosis?

Answer 26

Invagination and enclosure of organelles in vesicles, dissolving of DNA in nucleus by enzymes and engulfment of cell material and phagocytotic recycling

Question 27

How can P53 apoptosis be intrinsically regulated?

Answer 27

Activation of BID with induction of BAX to form pore structues in the MM

Question 28

How can P53 apoptosis be extrinsically regulated?

Answer 28

Induction of death receptors activated by cells expression Fas ligand