L06

Question 1

What is hypoxia

Answer 1

Lowering of oxygen conc. compared to the normal levels cells are exposed to

Question 2

What percentage of oxygen is considered normoxia?

Answer 2

20.9%

Question 3

What is the importance of studying hypoxia

Answer 3

involved in physiological and pathalogical processes

Question 4

What physiological processes is hypoxia involved in - embryo dev?

Answer 4

Hypoxia is responsible in embryo developments for the the placenta, heart, bone and vasculature.

Question 5

What physiological processes is hypoxia involved in - adaptation?

Answer 5

High alt. living, intense muscle exercise

Question 6

What areas of medicine are impacted by hypoxia?

Answer 6

High alt. diseases, cancer, arthritis, agening, diseases, schz., diabetes, stroke, kidni and GI.

Question 7

Did most people present with levels of hypoxia when diagnosed with COVID?

Answer 7

Yes

Question 8

What does hypoxia do that causes the cell to react?

Answer 8

DNA replication block, chromatin structure changes, txn. program, translational block, micorRNA signature.

Question 9

How does the cell respond to hypoxia?

Answer 9

Restoring O2 homeostasis, cell survival or cell death?

Question 10

What does HIF stand for?

Answer 10

Hypoxia Inducible Factor

Question 11

HIF is a heterdimeric TF. What 2 factors does it contain

Answer 11

HIF - alpha and 1beta.

Question 12

What are the three types of HIF-alpha?

Answer 12

1alpha - expressed in all tissues
2alpha - certain tissues, similar to 1 aplha
3alpha - certain tissues, lacks C terminus and acts as a dom. neg. inhibitor for 1alpha and 2alpha.

Question 13

What does the bHLH domain do?

Answer 13

Mediates DNA binding
(basic helix loop helix)

Question 14

What does the PAS domain mediate?

Answer 14

Dimerisation

Question 15

What does the C terminal domain do?

Answer 15

Transactivation domain

Question 16

What is the ODD?

Answer 16

Oxygen Dependant Degredation Domain

Question 17

What domain does the HIF-1beta lack?

Answer 17

ODD - oxygen dep. deg. domain

Question 18

Proline Hydroxylases regulate HIF require ____ to function.

Answer 18

Oxygen

Question 19

How do we convert proline to hydroxyproline?

Answer 19

Hydroxylase

Question 20

How is HIF1a regulated under normoxia?

Answer 20

The gene is transcribed continually, translated and in PostTxnRegulation OH groups are added on to HIF1a from PHD

Question 21

What does the hydroxylation of HIF1a do?

Answer 21

Creates a protein binding site of VHL

Question 22

What does the binding of VHL result in?

Answer 22

Ubquitilisation of the HIF1a, which is then degraded

Question 23

What does the stabilised HIF-1a bind to?

Answer 23

HIF-1b,

Question 24

What does the aspirigine hydroxylation do?

Answer 24

Blocks ability of HIF to interact w/Transcriptional activators (CBP)

Question 25

What happens in the absence of Aspg. OH?

Answer 25

HIF can interact w/TAC like CBP

Question 26

What pathways are controlled by HIF?

Answer 26

O2 supply, transcription, cell growth, cell death, cellular metabolism and HIF control

Question 27

Many solid tumours have hypoxic areas due to poor blood supply. True or False?

Answer 27

True

Question 28

What does the activation of HIF result in (cancer(

Answer 28

Growth of new blood vessels (angiogenesis) Bring nutrients and O2 to tumour

Question 29

HIF regulates the spread of tumour characteristics such as increased evasion, metasis and enhanced growth and survival.True or Flase

Answer 29

True.

Question 30

What are the different domains in the p53?

Answer 30

Transactivation domain (TAD) Proline rich romain Nuclear localisation sequence Tetramerisation domain

Question 31

What does p53 regulate

Answer 31

Tumour suppression, development, stem cell modulation and fertility

Question 32

What does p53 respond to?

Answer 32

DNA damage, cell cycle abnormalities and hypoxia

Question 33

What does DNA damage do?

Answer 33

Activates ATM kinase -> dissociates mdm2 and p53 complex -> activating p53 by inhibiting mdm2

Question 34

How does p53 respond to DNA damage?

Answer 34

Cell cycle arrest -> DNA repair -> cell cycle restart OR Apoptosis -> death and elimination of damaged cells

Question 35

When is p14ARF expressed

Answer 35

Expressed when oncogenes are activated

Question 36

What does the p14ARF do?

Answer 36

Directly binds to the inhibitor freeing p53 from the complex?

Question 37

Mdm2 is an E3 ligase. True or False

Answer 37

True

Question 38

What is the mdm2 feedback loop?

Answer 38

p53 stimulates Mdm2 gene expression forming a negative feedback loop that limits the extent of p53 activation.

Question 39

The role of negative feedbacl among TXN factor pathways

Answer 39

Provides mechanism to limit the period and intensity of the response tp a stimulus, Failure to induce these -vefdbk = death/disease p53 induces its IHB. Mdm2 = proteolytic deg. (PTD) HIF1a induces PHD that causes PTD NF-kB induces inhibitor that removes it from the nucleus and retains it in the cytoplasm

Question 40

What happens to p53 in cancer cells?

Answer 40

The pathway is inactivated, inhibiting p53 activity

Question 41

What are things that cause cancer?

Answer 41

Viral infection (Papilloma = cervical cancer) Mutation of ATM/ARF Amplification of MDM2 Mutation of p53 = loss of fx

Question 42

What are hotspots in p53?

Answer 42

Single amino acid changes that are frequently occurring in cancer

Question 43

What causes LFS syndrome

Answer 43

Genetic condition. Most commonly caused by a mutation in the TP53 gene which is the genetic blueprint for p53. Mutation takes away the genes ability to function correctly.

Question 44

What is the relationship between NF-kB and p53

Answer 44

Cross-regulate each other