L7 - p53 and cancer Flashcards

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1
Q

What is p53?

A

It is an unusual tumour suppressor gene that is mutated in most cancers

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2
Q

Are people heterozygous for p53 more or less likely to get cancer?

A

More likely

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3
Q

What is confirmation specificity?

A

It is when an ab only recognises a protein in a specific confirmation. In the case of p53, when it is mutated it undergoes a cc and can only be recognised by certain abs

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4
Q

Why is it important that p53 has tetrameric structure?

A

If 1 su of the 4 is not functional then the protein won’t work. This explains why if you have an exogenous mutant p53 and 2 copies of the endogenous p53 you will still see a mutant phenotype

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5
Q

What factors upregulate p53 expression?

A

Lack of nucleotides, UV radiation, ionising radiation, oncogene signalling, hypoxia, blockage of transcription

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6
Q

What are the target genes of p53?

A

p53 upregulates expression of genes that block entry into cell cycle to allow DNA repair or apoptosis if necessary

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7
Q

What keeps p53 levels low?

A

Short half life and MDM2

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8
Q

What is the role of MDM2?

A

It is a ubiq ligase that tags p53 for destruction in the proteaosome. p53 also reg the levels of trsc MDM2, high levels of p53 = increased trsc of MDM2

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9
Q

What keeps p53 levels high?

A

Arf - binds MDM2 and sequesters it in the nucleolus

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10
Q

What effects do genotoxic stress have on p53 levels?

A

Increase in p53 levels due to the activation of ATM/ATR which phos p53 - active form

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11
Q

What happens when p53 is inact in cancer cells?

A
  • oncogene activation without apoptosis
  • higher tolerance to anoxia
  • sloppy oversight of chr. integrity
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12
Q

What activates ATM?

A

Double stranded breaks

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13
Q

What activates ATR?

A

Issues with DNA replication - when DNA replication fork is affected

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14
Q

How can p53 reactivation be used?

A

Mutant p53 have an altered shape
Can screen for drugs that bind and alter p53 shape
Confirmation specific antibodies to check if drugs have altered the p53 shape
e.g. PRIMA 1
- increased number of cells in G2 - DNA repairing
- increased number of cells below G1 - this is the apoptotic population

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