49. TUMOUR SUPPRESSOR GENES Flashcards

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1
Q
  1. What do the Tumour Suppressor Genes control?
A
  • the Cell Cycle
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2
Q
  1. What inhibits Cell Division?
A
  • the protein products of the Tumour Suppressor
    Genes
  • they prevent the uncontrolled Growth that
    contributes to cancer
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3
Q
  1. What are two very important Tumour Suppressor Genes?
A
  1. RB1
  2. TP53
  • these produce Rb and p53 proteins
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4
Q
  1. What is p53 the Gate Keeper of?
A
  • the CDK Inhibitor
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5
Q
  1. What is Rb?
A
  • this is the Retinblastoma Protein
  • it is a tumour suppressor gene
  • it codes for the tumour suppressor protein
  • it inhibits the cell cycle progression
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6
Q
  1. What does Rb inhibit?
A
  • E2F activation during G1
  • it does this by first isolating E2F
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7
Q
  1. How is Rb regulated during the G1 Phase?
A
  • Rb is dephosphorylated by the PP-1 protein
  • the Protein Phosphatase 1
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8
Q
  1. At the end of the G1 Phase, how is Rb regulated?
A
  • the Cyc-cdks phosphorylate Rb
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9
Q
  1. What kind of Rb cannot isolate E2F?
A
  • Phosphorylated Rb
  • this means that E2F is released
  • E2F is activated
  • the cell then enters the S Phase
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10
Q
  1. What is Retinoblastoma?
A
  • it is a malignant tumour
  • it can occur in one eye (Unilateral)
  • it can occur in both eyes (Bilateral)
  • it typically occurs in children that are less than 5
    years old
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11
Q
  1. Where does Retinablastoma originate from?
A
  • the Retina
  • this is the sensitive lining of the eye
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12
Q
  1. How many children World Wide develop Retinablastoma?
A
  • about 6000 children
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13
Q
  1. How many births are affected by Retinoblastoma?
A
  • 1 out of 15 000
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14
Q
  1. What are the two forms of Retinoblastoma?
A
  1. Familial (Heritable) Retinoblastoma
  2. Sporadic (Non-Heritable) Retinoblastoma
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15
Q
  1. What causes Retinoblastoma?
A
  • the mutation in the Tumour Suppressor Gene
    RB1
  • this encodes for the Rb protein
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16
Q
  1. What are Cdk Inhibitors (CKIs)?
A
  • they inhibit the activity of the Cyclin-Cdk
    complexes
  • they are enzymes
17
Q
  1. What are the 2 major categories of Cdk Inhibitors?
A
  1. INK4Family
  2. Cip/Kip Family
18
Q
  1. What Cdk Inhibitors are found in the INK4 Family?
    What do they do?
A
  • they inhibit the activity of the G1 cyclin cdks

SUCH AS:
- cyc-D/cdk-4
- cyc-D/cdk-6

19
Q
  1. What Cdk Inhibitors are found in the Cip/Kip family?
    What do they do?
A
  • they inhibit the activity of all the other Cyc-cdk complexes
  • this is known as late G1-M

SUCH AS:
- cyc-E/cdk-2
- cyc-A/cdk-2

20
Q
  1. What is the expression of Cdk Inhibitors expressed by?
A
  • it is strongly stimulated by the DNA damage
  • and by p53 Activation
21
Q
  1. How present is p53 in our blood?
A
  • p53 is found at very low levels in the blood
  • it is found in very low levels in normal cells
  • there would be no cell division if p53 was active
    all the time
22
Q
  1. Which enzyme activates p53?
A
  • Kinase
23
Q
  1. What destructs p53?
A
  • Proteasomes
24
Q
  1. What are the 3 functions of p53?
A
  1. the Expression of CKIs
    - this leads to Cell Cycle Arrest
    - it induces G1-G2 cell cycle repair
  2. DNA Repair
    - an example of this is Excision Repair
    - p53 detect DNA damage
  3. Apoptosis
    - this is when repairs are not possible
    - the damage to the DNA is too severe
    - the cell commits suicide
25
Q
  1. What is the TP53 gene known as?
A
  • The Guardian of the Genome
  • a mutation of this gene is found in most cancers
    (over 50%)
26
Q
  1. What does the TP53 gene encode for?
A
  • it encodes for the p53 protein
27
Q
  1. What is the most commonly affected Tumour Suppressor gene in Human Cancer?
A
  • TP53
28
Q
  1. What two types of signals control the Cell Cycle Progression at Checkpoints?
A
  1. Internal Signals
  2. External Signals
29
Q
  1. What are some examples of Internal Signals?
A
  • cell size
  • incorrect alignment
  • separation of sister chromatids

NB:
- this all happens at the M Phase Checkpoint

30
Q
  1. What are some examples of External Signals?
A
  • environmental conditions
  • presence of growth factors
31
Q
  1. What do Growth Factors stimulate?
A
  • they stimulate other cells to divide
32
Q
  1. What does PDGF stimulate?
A
  • PDGF is a Platelet Derived Growth Factor
  • it stimulates Fibroblast growth in a wound or a
    culture
33
Q
  1. What are Density-Dependent Inhibition?
A
  • crowded cells stop dividing
34
Q
  1. What is Anchorage Dependence?
A
  • most animal cells must be attached to a
    substratum (support) in order to divide

SUBSTRATUM:
- a foundation or basis of something
- an underlying layer or substance

35
Q
  1. What limits cell density to only existing as a single layer in Normal Mammalian cells?
A
  • the availability of nutrients
  • the availability of growth factors
  • a substratum for attachment
36
Q
  1. What happens during Anchorage Dependence?
A
  • the cells anchor to the dish surface
  • they divide
37
Q
  1. What is meant by Density-Dependent Inhibition?
A

CELLS WILL STOP DIVIDING:
- when they have formed a complete single layer

IF SOME CELLS ARE SCRAPED AWAY:
- the remaining cells will divide to fill the gap
- these cells then stop