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CMB2001 > L06 > Flashcards

L06 Flashcards

1
Q

What is hypoxia

A

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

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2
Q

What percentage of oxygen is considered normoxia?

A

20.9%

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3
Q

What is the importance of studying hypoxia

A

involved in physiological and pathalogical processes

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4
Q

What physiological processes is hypoxia involved in - embryo dev?

A

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

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5
Q

What physiological processes is hypoxia involved in - adaptation?

A

High alt. living, intense muscle exercise

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6
Q

What areas of medicine are impacted by hypoxia?

A

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

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7
Q

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

A

Yes

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8
Q

What does hypoxia do that causes the cell to react?

A

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

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9
Q

How does the cell respond to hypoxia?

A

Restoring O2 homeostasis, cell survival or cell death?

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10
Q

What does HIF stand for?

A

Hypoxia Inducible Factor

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11
Q

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

A

HIF - alpha and 1beta.

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12
Q

What are the three types of HIF-alpha?

A

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.

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13
Q

What does the bHLH domain do?

A

Mediates DNA binding
(basic helix loop helix)

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14
Q

What does the PAS domain mediate?

A

Dimerisation

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15
Q

What does the C terminal domain do?

A

Transactivation domain

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16
Q

What is the ODD?

A

Oxygen Dependant Degredation Domain

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17
Q

What domain does the HIF-1beta lack?

A

ODD - oxygen dep. deg. domain

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18
Q

Proline Hydroxylases regulate HIF require ____ to function.

A

Oxygen

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19
Q

How do we convert proline to hydroxyproline?

A

Hydroxylase

20
Q

How is HIF1a regulated under normoxia?

A

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

21
Q

What does the hydroxylation of HIF1a do?

A

Creates a protein binding site of VHL

22
Q

What does the binding of VHL result in?

A

Ubquitilisation of the HIF1a, which is then degraded

23
Q

What does the stabilised HIF-1a bind to?

A

HIF-1b,

24
Q

What does the aspirigine hydroxylation do?

A

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

25
Q

What happens in the absence of Aspg. OH?

A

HIF can interact w/TAC like CBP

26
Q

What pathways are controlled by HIF?

A

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

27
Q

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

A

True

28
Q

What does the activation of HIF result in (cancer(

A

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

29
Q

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

A

True.

30
Q

What are the different domains in the p53?

A

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

31
Q

What does p53 regulate

A

Tumour suppression, development, stem cell modulation and fertility

32
Q

What does p53 respond to?

A

DNA damage, cell cycle abnormalities and hypoxia

33
Q

What does DNA damage do?

A

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

34
Q

How does p53 respond to DNA damage?

A

Cell cycle arrest -> DNA repair -> cell cycle restart

OR

Apoptosis -> death and elimination of damaged cells

35
Q

When is p14ARF expressed

A

Expressed when oncogenes are activated

36
Q

What does the p14ARF do?

A

Directly binds to the inhibitor freeing p53 from the complex?

37
Q

Mdm2 is an E3 ligase. True or False

A

True

38
Q

What is the mdm2 feedback loop?

A

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

39
Q

The role of negative feedbacl among TXN factor pathways

A

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

40
Q

What happens to p53 in cancer cells?

A

The pathway is inactivated, inhibiting p53 activity

41
Q

What are things that cause cancer?

A

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

42
Q

What are hotspots in p53?

A

Single amino acid changes that are frequently occurring in cancer

43
Q

What causes LFS syndrome

A

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.

44
Q

What is the relationship between NF-kB and p53

A

Cross-regulate each other

45
Q
A

CMB2001 (8 decks)

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