Cell Cycle, Apoptosis, and Cancer Flashcards

1
Q

When is the restriction point (R), and what happens there?

A

2 hours prior to S phase (in G1)

if growth factors are limiting –> restriction occurs

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2
Q

What two proteins in HPV cause cancer?

A

E6 and E7

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3
Q

What happens in the G0 phase?

A

poor nutrient/environmental conditions –> cell withdraws from cell cycle

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4
Q

What do proto-oncogenes normally code for?

A

growth factors
receptors for GFs and hormones
Transcription factors
(basically anything promoting cell growth and division)

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5
Q

What is p53

A

transcription factor that is activated when DNA is damaged –> activates p21 –> keeps Rb hypophosphorylated and sequesters E2F so you can’t move into S phase
Promotes apoptosis = tumor suppressor

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6
Q

What does CDC25 phosphatase do?

A

Undoes WEE1 phosphorylation of C-CDK complex to reactivate it

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7
Q

When do topoisomerase I inhibitors work?

A

S, G2, and M phases

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8
Q

What does E6 in HPV inhibit?

A

p53

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9
Q

What are the checkpoints?

A

R, G1, G2, Metaphase

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10
Q

What is APC/C?

A

anaphase promoting complex/ cyclosome
a ubiquitin ligase enzyme that adds polyubiquitin to cdk-cyclin complex –> cyclin degrades –> signals change to anaphase

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11
Q

What type of protein is APC?

Mutations in it are linked to what type of cancer?

A

adenomatous polyposis coli = tumor suppressor

colon cancer

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12
Q

What does the SH2 domain on GRB-2 do?

A

binds to phosphorylated tyrosine residues on an RTK

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13
Q

What are 2 common toxins that cause p53 mutations?

A

activated benzopyrene in cigarette smoke and aflatoxin, a fungal metabolite in moldy grain and peanuts

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14
Q

What happens in the G2 phase?

A

DNA stability is checked

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15
Q

How do alkylating agents work to treat cancer?

A

block DNA replication

affect all phases of cell cycle

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16
Q

How to antimetabolites work to treat cancer?

A

inhibit enzymes involved in DNA synthesis

S phase

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17
Q

What is Erbitux?

A

treats colorectal cancer

mAb directed against EGF receptor that is over-expressed in colorectal cancer

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18
Q

What triggers metaphase to anaphase?

A

cyclin turnover

APC/C degrades cyclin to help do this

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19
Q

What is the order of the cell cycle?

A

G0 G1 –> S –> G2 –> M

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20
Q

What happens in the M phase

A

Mitosis
Chromosome separation
Cell division

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21
Q

What happens in the G1 checkpoint?

A

occurs in response to DNA damage

timing similar to R (2 hours before S)

22
Q

What happens in hereditary retinoblastoma?

A

mutation/deletion of once copy of RB1 is inherited –>

cells are predisposed to be cancerous –> some mutation occurs to eliminate last good copy –> cancer

23
Q

How can viruses cause cancer?

A

During virus replication, accidentally incorporates a human proto-oncogene into its genome –> mutation turns it into an oncogene –> virus can now transform normal cells and cause cancer

24
Q

Which enzyme is missing in many somatic cells that causes their senescence?

A

telomerase - maintains telomere length

w/out it, telomeres shrink and cells will eventually die

25
What type of mutations turn proto-oncogenes into oncogenes?
gain of function mutations --> increased expression of protein products expression of altered protein (oncoprotein) that doesn't respond to normal signal
26
What is cyclin A essential for?
so that S phase can occur
27
What happens in the G1 phase?
RNA and protein synthesis needed for DNA replication
28
What does p27 do?
Inhibits cyclin-CDK by binding to it
29
What do small G-proteins do, and what is their significance with cancer?
monomeric G proteins that have GTPase activity (RAS); control cell proliferation; apoptosis, and a lot of other stuff; mutations can lead to cancer
30
How to cytotoxic antibiotics work to treat cancer?
intercalate between bases in DNA to inhibit DNA synthesis | S phase and G2 phase
31
What type of protein is p53?
Tumor suppressor
32
What types of cancers do mutations in p53 cause?
65% of colon cancers 30-50% of breast cancers 50% of lung cancers others
33
What does Herceptin do?
treats breast cancer; is a monoclonal Ab for HER2/NEU
34
What does E7 in HPV inhibit?
Rb
35
What do metastasis suppressors do?
cell adhesion proteins that prevent tumor cells from dispersing and block loss of contact inhibition
36
How to mitotic inhibitors work to treat cancer?
Arrest cells in mitosis during metaphase
37
What happens in the metaphase checkpoint?
ensures chromosomes are attached to mitotic spindle
38
How are gain of function mutations in proto-oncogenes passed on?
autosomal dominant
39
What is HER2?
Proto-oncogene that, when mutated, results in overexpression of HER2 observed in many breast cancers
40
What type of protein is PTEN? | Mutations in it are linked to what type of cancer?
tumor suppressor | Prostate cancer
41
What does WEE1 Kinase do?
Inhibits Cyclin-CDK complex by hyperphosphorylating it
42
What type of mutations screw up tumor suppressors?
loss of function
43
What happens in the S phase?
DNA Synthesis
44
What type of protein is retinoblastoma (Rb)?
tumor suppressor
45
What does cyclin E do?
gets cell from G1 to S
46
How are loss of function mutations in tumor suppressor genes passed on?
autosomal recessive | only need 1 good copy to function
47
What happens in G2 checkpoint?
Verify complete genomic duplication
48
What is Gleevec?
treats chronic myelogenous leukemia | binds to active site of ABL tyrosine kinase and inhibits its activity
49
What is the most common base change in p53 that causes cancer?
G --> T transversion
50
What is p21?
tumor suppressor that inhibits cyclin-CDK by keeping Rb hypophosphorylated so E2F is sequestered and can't go into S phase