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Cell Proliferation and Underlying diseases > The Cell Cycle > Flashcards

The Cell Cycle Flashcards

1
Q

What are the 4 stages of the cell cycle?

A

G1
S
G2
M

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2
Q

What is the function of the M phase?

A

Make sure the chromosomes are attached at the appropriate locations

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3
Q

When are cells quiescent (inactive)?

A

G0

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4
Q

What are the checkpoints of the cell cycle?

A

G1/S checkpoint
S checkpoint
G2/M checkpoint
M checkpoint

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5
Q

What is the function of G1?

A

Cells undergo the cell cycle in the presence of growth factors. G1 is involved in commitment and restriction, ensures there I should enough growth fa tor for Thebes whole cycle.

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6
Q

What two types of instability are involved in cancer?

A

Genomic instability

Chromosomal instability

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7
Q

What two homologise are needed for replication and mitosis?

A

CDC28 and CDC2

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8
Q

What protein is involved in Sea Urchin and Xenopus Oocyte cell division?

A

Cyclins

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9
Q

What is M-phase Promoting Factor (MPF)?

A

A cyclin dependents protein kinase
Consists of:
- CDC2 (catalytic subunit)
- Cyclin B

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10
Q

What is the experiment for MPF?

A

Oocyte is treated with progesterone and stats to divide
Took the cytoplasm of the Oocyte and inject it into an Oocyte G2 arrested cell
They progress into M phase

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11
Q

Describe the cyclin-dependent protein kinase

A

1) cyclin binds to an inactive protein kinase
2) protein kinase is activated
3) binds to substrate
4) phosphorylate substrate

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12
Q

What is another name for MPF?

A

Cdk1-CyclinB

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13
Q

When are Cdk1-CyclinB levels high?

A

During M phase

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14
Q

When are Cdk1-CyclinB levels low?

A

During S phase

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15
Q

Explain CyclinB patterns in the cell cycle

A

Increase gradually and then drop after M phase

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16
Q

What CDKs and cyclins are present in G1?

A

Cyclin D1-3

CDK4 and 6

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17
Q

What CDKs and cyclins are present in late G1?

A

Cyclin E

CDK2

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18
Q

What CDKs and cyclins are present in S-M?

A

CyclinA

CDK1 and 2

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19
Q

What CDKs and cyclins are present in G2-M?

A

Cyclin B1 and B2

CDK1

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20
Q

Name a transcription factor involved in genes required for DNA synthesis

A

E2F-DP1

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21
Q

What’s controls E2F-DP1?

A

Retina blastoma proteins (RB) - negative regulator

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22
Q

What does the repressor complex contain?

A

RB
HDAC
SNF
SWI

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23
Q

How is the repressor complex released?

A

Phosphorylated at two locations on the RB

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24
Q

What is RB?

A

A tumour suppressor involves in a rare eye cancer

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25
What can RB be targeted by to get cancer?
DNA tumour viruses e.g. SV40
26
Types of CDK inhibitors
``` INK4 family (inhibitors of kinase 4) - G1 phase inhibitors CIP/KIP family - S phase inhibitors ```
27
Roles of CDK inhibitors
Lineage-specific roles Roles in regulating stem cell proliferation p16 regressed epigenetically and reactivated during senescence
28
What is senescence?
Perminant withdrawak from the cell cycle into G0
29
How do growth factors start the cell cycle?
Activate signalling cascades which leads to transcription of Cyclin D (mitogen dependent)
30
What does Cyclin D interact with?
CDK4 and 6 | P27KIP1
31
Effect of p27 on Cyclin D, CDK4 and 6
No effect, it does not inhibit them | Acts as a scaffolding protein
32
What do CyclinD-CDK4/6 do?
Isolate p27KIP1 and phosphorylated RB
33
What does cyclinD-CDK4/6-dependent phosphorylation of RB cause?
CyclinE expression
34
Function of CyclinE/CDK2
Further phosphorylated RB causes expression of genes for DNA synthesis Phosphorylated p27KIP1 to target it for degradation (Mitogen independent)
35
What are the oncogenes in the ERK pathway?
Receptor tyrosine kinase Ras Raf CyclinD1
36
Which Cyclin does the ERK pathway cause expression of?
CyclinD1
37
Effect of p27 on CyclinE-CDK2?
Inhibits it
38
What does p16INK4A
CDK4/6
39
What cancers are related to mutations in?
Melanoma | Pancreatic cancer
40
What is the inhibitor of Mdm2?
P19ARF in mice | P14ARF in humans
41
What is the function of Mdm2?
Inhibit p53
42
What is the function of p53 on Mdm2?
Activates it, negative feedback loop
43
What does p53 regulate?
P21
44
Name two growth arrest genes
14-3-3 sigma
45
What are all of the types of things p53 can do?
Repair Apoptosis Growth arrest Angiogenesis block
46
What kinases are involved in inhibiting Mdm2 due to DNA damage?
ATR | ATM
47
What kinase is involved in inhibiting Mdm2 due to UV damage?
ATR
48
What inhibitor inhibits Mdm2 due to oncogenes?
P14ARF
49
What complex causes c-Myc?
Smad4 Phosphorylated Smad3 x2 P107 E2F4/5
50
What are Smad3 Smad4 complexes
Transcriptional regulators of TGFbeta signalling
51
Where do p107 and E2F4/5 bind?
Smad response element
52
What do phosphorylated Smad3 x2 and Smad 4 bind to under p15 induction?
Fox C/EBPbeta
53
What do phosphorylated Smad3 x2 and Smad 4 bind to under p21 induction?
FOXO - inhibited by PI3K and FoxG1 RUNX3 Through MAPK signalling RUNX3
54
Inhibitor of p15 and p21
c-Myc
55
TGFbeta transcriptions factor inhibitors
p21WAF1 | p15INK4B
56
What cancer is HPV related to?
Cervical cancer
57
How does HPV cause cancer
1) expression of mutant gene E7 in the G1 phase which binds to RB. 2) RB releases the E2F-DP1 complex 3) progression into cell cycle 4) E6 binds to p53 and targets it for degradation
58
Pathways regulating senescence-mediated arrest
``` Telomere erosion Oncogene overexpression ROS mediated DNA damage Mitochondrial dysfunction Inflammation ```
59
4 protein kinase which control G2 and M
CDK1 CDK7 PLK1 Aurora A
60
What is the inactive form of CDK1?
T14 phosphorylation by MYT1 | Y15 phosphorylation by WEE1
61
What does the dephosphorylation of T14 and Y15 cause?
Activation of CDK7 through binding to Cyclin H and allows phosphorylation of T161
62
Effect of DNA damage in the G2/M checkpoint
1) ATM activated (activate so p53) 2) Chk2 activate d (activates p53) 3) Cdc25 phosphorylated 4) Cdc25 binds to 14-3-3sigma protein 5) Cdc25 sequestered into the cytoplasm by 14-3-3
63
What ubqituitin ligand polyubiquitinates Cyclin B?
APC/C
64
Inhibitor of APC/C
SAC
65
What two CDKs are needed to make a a sterile rat?
CDK 1 and 4
66
Technique used to measure the cell cycle
Flow-activated cell sorter (FACS)
67
How does a FACSIMILE work?
1) grow cells on a dish 2) fix cells 3) harvest cells 4) add propidium iodide and incubate 5) calculate the relative amound of fluorescence
68
Function of propidium iodide
DNA intercalator | Binds to DNA in cells and adds fluorescence

Cell Proliferation and Underlying diseases (12 decks)

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