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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
Q

What can RB be targeted by to get cancer?

A

DNA tumour viruses e.g. SV40

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26
Q

Types of CDK inhibitors

A 
INK4 family (inhibitors of kinase 4) - G1 phase inhibitors 
CIP/KIP family - S phase inhibitors
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27
Q

Roles of CDK inhibitors

A

Lineage-specific roles
Roles in regulating stem cell proliferation
p16 regressed epigenetically and reactivated during senescence

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28
Q

What is senescence?

A

Perminant withdrawak from the cell cycle into G0

29
Q

How do growth factors start the cell cycle?

A

Activate signalling cascades which leads to transcription of Cyclin D (mitogen dependent)

30
Q

What does Cyclin D interact with?

A

CDK4 and 6

P27KIP1

31
Q

Effect of p27 on Cyclin D, CDK4 and 6

A

No effect, it does not inhibit them

Acts as a scaffolding protein

32
Q

What do CyclinD-CDK4/6 do?

A

Isolate p27KIP1 and phosphorylated RB

33
Q

What does cyclinD-CDK4/6-dependent phosphorylation of RB cause?

A

CyclinE expression

34
Q

Function of CyclinE/CDK2

A

Further phosphorylated RB causes expression of genes for DNA synthesis
Phosphorylated p27KIP1 to target it for degradation
(Mitogen independent)

35
Q

What are the oncogenes in the ERK pathway?

A

Receptor tyrosine kinase
Ras
Raf
CyclinD1

36
Q

Which Cyclin does the ERK pathway cause expression of?

A

CyclinD1

37
Q

Effect of p27 on CyclinE-CDK2?

A

Inhibits it

38
Q

What does p16INK4A

A

CDK4/6

39
Q

What cancers are related to mutations in?

A

Melanoma

Pancreatic cancer

40
Q

What is the inhibitor of Mdm2?

A

P19ARF in mice

P14ARF in humans

41
Q

What is the function of Mdm2?

A

Inhibit p53

42
Q

What is the function of p53 on Mdm2?

A

Activates it, negative feedback loop

43
Q

What does p53 regulate?

A

P21

44
Q

Name two growth arrest genes

A

14-3-3 sigma

45
Q

What are all of the types of things p53 can do?

A

Repair
Apoptosis
Growth arrest
Angiogenesis block

46
Q

What kinases are involved in inhibiting Mdm2 due to DNA damage?

A

ATR

ATM

47
Q

What kinase is involved in inhibiting Mdm2 due to UV damage?

A

ATR

48
Q

What inhibitor inhibits Mdm2 due to oncogenes?

A

P14ARF

49
Q

What complex causes c-Myc?

A

Smad4
Phosphorylated Smad3 x2
P107
E2F4/5

50
Q

What are Smad3 Smad4 complexes

A

Transcriptional regulators of TGFbeta signalling

51
Q

Where do p107 and E2F4/5 bind?

A

Smad response element

52
Q

What do phosphorylated Smad3 x2 and Smad 4 bind to under p15 induction?

A

Fox

C/EBPbeta

53
Q

What do phosphorylated Smad3 x2 and Smad 4 bind to under p21 induction?

A

FOXO - inhibited by PI3K and FoxG1
RUNX3
Through MAPK signalling RUNX3

54
Q

Inhibitor of p15 and p21

A

c-Myc

55
Q

TGFbeta transcriptions factor inhibitors

A

p21WAF1

p15INK4B

56
Q

What cancer is HPV related to?

A

Cervical cancer

57
Q

How does HPV cause cancer

A

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
Q

Pathways regulating senescence-mediated arrest

A 
Telomere erosion 
Oncogene overexpression 
ROS mediated DNA damage 
Mitochondrial dysfunction 
Inflammation
59
Q

4 protein kinase which control G2 and M

A

CDK1
CDK7
PLK1
Aurora A

60
Q

What is the inactive form of CDK1?

A

T14 phosphorylation by MYT1

Y15 phosphorylation by WEE1

61
Q

What does the dephosphorylation of T14 and Y15 cause?

A

Activation of CDK7 through binding to Cyclin H and allows phosphorylation of T161

62
Q

Effect of DNA damage in the G2/M checkpoint

A

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
Q

What ubqituitin ligand polyubiquitinates Cyclin B?

A

APC/C

64
Q

Inhibitor of APC/C

A

SAC

65
Q

What two CDKs are needed to make a a sterile rat?

A

CDK 1 and 4

66
Q

Technique used to measure the cell cycle

A

Flow-activated cell sorter (FACS)

67
Q

How does a FACSIMILE work?

A

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
Q

Function of propidium iodide

A

DNA intercalator

Binds to DNA in cells and adds fluorescence

Cell Proliferation and Underlying diseases (12 decks)

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