(7) Cell Cycle, Apoptosis and Cancer Flashcards

1
Q

Broad overview of the cell cycle?

A
  1. Cell growth and chromosome replication
  2. Chromosome segregation
  3. Cell division
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2
Q

What are the stages of the cell cycle?

A
  1. The S Phase (Synthesis)

2. The M Phase (Mitosis)

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3
Q

Insert stages of the cell cycle here!!!

A

Slide 7

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4
Q

The Stages of the cell cycle:

What occurs in MITOSIS (M):

A
  • Nuclear division (mitosis) at the beginning

- Cell division (cytokinesis) at the end

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5
Q

The Stages of the cell cycle:

What occurs in interphase?

A

(G1): Gap 1 phase; RNA and protein synthesis needed for DNA replication

(S): DNA synthesis

(G2): Gap 2 phase- DNA stability is checked

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6
Q

The Stages of the cell cycle:

What occurs during Go phase?

A

Occurs during POOR NUTRIENT/enviornmental conditions

–> Cells withdraw from cell cycle

*Also occurs following terminal differentiation in certain tissue types

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7
Q

The Stages of the cell cycle:

What are restriction points/checkpoints for?

A

A discrete timepoint where “errors” are checked

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8
Q

The Stages of the cell cycle:

___ Restriction point
___ Checkpoints

A

one restriction point; 3 checkpoints

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9
Q

The Stages of the cell cycle:

What happens if growth factors are limiting?

A

Growth factors are limiting

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10
Q

The Stages of the cell cycle:

Progression following exit from restriction point (R) is growth factor _________

A

independent

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11
Q

The Stages of the cell cycle:

G1 checkpoint

Occurs in response to:

A

DNA Damage

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12
Q

The Stages of the cell cycle:

G2 checkpoint

Purpose?

A

Verify complete genomic duplication

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13
Q

The Stages of the cell cycle:

Metaphase checkpoint

Purpose?

A

Ensures chromosomes attached to mitotic spindle

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14
Q

Cell cycle is activated by ______

A

growth factors

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15
Q

Retinoblastoma (Rb) and Cyclin activity: Describe

A

Rb and E2F are associated with each other. Cyclin D-CDK4 and Cyclin D-CDK6 can hyperphosphorylate RB to dissociate it from E2F…

Then, E2F can actively transcribe

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16
Q

____________ drives cells from G1 to S phase of the cell cycle

A

Rb Phosphorylation

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17
Q

Once E2F is actively transcribing, what does it produce?

A

Cyclin E: cell cycle goes from G1 to S phase

Cyclin A: S phase can occur

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18
Q

Retinoblastoma protein is known as a __________ protein

A

tumor suppressor

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19
Q

What are activators of cyclin-CDK activity?

A

-Binding of cyclin to CDK causes only PARTIAL activation

***FULL activation=CDK activating kinase (CAK)

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20
Q

What are inhibitors of Cyclin-CDK activity?

A
  • p27

- WEE1

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21
Q

Cdk-activating kinase (CAK) and the T-Loop

What’s its role?

A

T-loop is a region of CDK that blocks active site

  • T-loop moves out of active site after cyclin binding
  • CAK phosphorylates T-loop which FULLY activates enzyme
22
Q

What specific cyclins help the passage of cells through the restriction point in late G1 phase?

A

Cyclin D-CDK4

CyclinD-CDK6

23
Q

What are the methods to regulate Cyclin-Cdk activities?

A
  1. Phosphorylation of CDK
  2. Binding of CKI (p27/WEE1)
  3. Proteolysis of cyclins
24
Q

What can make a Cyclin-CDK complex fully active after being hyperphosphorylated?

A

CDC25 phosphatase

25
p53 is the...
"Guardian of the genome" -A transcription factor
26
p53 In the absence of DNA damage...
MDM2 degrades p53
27
p53 In the presence of DNA damage...
Activates protein kinases that phosphorylate p53 (*ACTIVATES) - Increased transcription of p21 - CKI
28
Extrinsic pathway: What is the caspase associated?
Procaspase 8 --> Caspase 8
29
Extrinsic pathway: AKA?
Death receptor pathway; triggered by binding of external death ligand
30
Extrinsic pathway: What are examples of external death ligands?
Fas ligand, TNFalpha (tumor necrosis factor)
31
Extrinsic pathway: What happens after caspase 8 becomes active?
Activates caspases -3, -6, -8
32
Intrinsic pathway: AKA?
Mitochondrial pathway
33
Intrinsic pathway: What causes it?
Triggered by: Growth factor withdrawal, DNA damage, cell cycle defects
34
Intrinsic pathway: How does it happen?
Cytochrome C released by stressed mitochondria, binds to n
35
Intrinsic pathway: How does it happen?
Cytochrome C released by stressed mitochondria Binds to an adaptor protein (APAF-1) Leads to Apoptosome Recruits Caspase 9
36
Intrinsic pathway: What can facilitate?
*Proapoptotic BAX BAK p53
37
Intrinsic pathway: What can inhibit?
*Antiapoptotic BCL-2 BCL-xl
38
How can a proto-oncogene be converted to oncogenes?
3 mechanisms 1. Point mutation/deletion 2. Gene amplification 3. Chromosomal translocation
39
What is an example of a common oncogene?
HER2 Receptor OVEREXPRESSED HER2, observed in many breast cancers
40
What is the major example of a tumor suppressor with a clinical correlation in the lecture?
Retinoblastoma (Rb)
41
What is the difference b/w sporadic retinoblastoma and hereditary?
Sporadic= RARE, 2 independent mutations of Rb Hereditary= Mutation/deletion of one copy of RB1, predisposed to be cancerous
42
What are the functions of tumor suppressors?
- Repress cell cycle progression - Promote apoptosis - DNA repair proteins (BRCA)
43
Name some other tumor suppressors:
1. RB1 --> Rb 2. TP53--> p53 3. PTEN; Phosphatase and tensin homolog 4. APC; adenomatous polyposis coli
44
What is the function of metastasis suppressors?
*Cell adhesion proteins - Prevent tumor cells from dispersing - Block loss of contact inhibition - Inhibit tumor metastasis
45
T/F You can get cancer from a single hit of a tumor suppressor gene
FALSE! You need multiple pathways to fail in order to cause cancer
46
HPV: E6 binds to
p53
47
HPV: p53 binds to
E6
48
HPV: E7 binds to
Rb
49
HPV Rb binds to
E7
50
What does GLEEVEC do?
- Competitive inhibitor of Bcr/c-Abl enzyme which is derived from the philadelphia chromosome 22/9 translocation, which stops the cell cycle * Anti-cancer
51
What is the mechanism of Erbitux?
EGF INHIBITOR