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Cancer Biology and Therapy > Sustaining proliferative signals > Flashcards

Sustaining proliferative signals Flashcards

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AP® Biology flashcards Biology 101 flashcards
1
Q

what is the cell cycle stimulated by?

A

extracellular signals inducing cell division

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2
Q

which extracellular signals induce cell division?

A

TK
tumour growth factor beta
intergrins
nutrient status

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3
Q

how many phases is the cell cycle divided into? name them

A 
4
G1
S
G2
M
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4
Q

how long does the G1 phase last?

A

6-12 hours

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5
Q

what happens in the G1 phase?

A

the cells growth and the chromosomes prepare for replication

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6
Q

where is the restriction point?

A

at the end of the G1 phase

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7
Q

what happens at the restriction point?

A

beyond this point the cells are committed to cell cycle progression

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8
Q

how long does the S phase last?

A

6-8 hours

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9
Q

what occurs in the S phase?

A

cells synthesise DNA

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10
Q

what happens in the G2 phase?

A

cells prepare for mitosis

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11
Q

how long does the G2 phase last?

A

3-4 hours

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12
Q

what is G0

A

non growing phase- called quiescent phase

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13
Q

order of mitosis phases?

A

prophase
prometaphase
metaphase
anaphase

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14
Q

what happens in prophase?

A

chromatin condenses and the process which separates the duplicated genetic material initiates

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15
Q

what occurs in pro metaphase

A

nuclear envelope breaks down

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16
Q

what occurs in metaphase

A

chromosomes align themselves in the centre of the cell
chromatids remain joined at the centromere

kinetochore microtubules pull the sister chromatids back and forth till they align along the centre

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17
Q

what are kinetochores and what do. they do?

A

protein filaments

extend from the poles of the cell and attach to the centromeres

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18
Q

what occurs in anaphase?

A

each pair of chromosomes are separated into 2 identical independent chromosomes
the sister chromatids are separated simultaneously at the centromeres and pulled to opposite ends of the cell

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19
Q

what separates chromosomes?

A

mitotic spindle

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20
Q

explain telophase?

A

separatess the duplicated genetic material into 2 separate cells
nuclear membrane forms around the chromosomes to separate them from the cytoplasm
chromosomes uncoil

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21
Q

what is cytokinesis

A

divides the cytoplasm of the cell

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22
Q

what type of proteins regulate cell cycle progression?

A

proteins which except kinase activity

23
Q

what are the kinases which aid cell cycle progression?

A

cyclins

cyclin dependent kinases

24
Q

what are cyclin dependent kinases and how do they contribute to the cell cycle?

A

family of serine/ threonine protein kinases triggered at specific points of the cell cycle, ensuring synchronised transition through the cell cycle

25
Q

MOA: how do cyclin/ CKD complexes regulate cell cycle progression?

hint: restriction point and talk about the kinases at each phase of the cell cycle?

A

before the restriction point in early G1, extracellular mitogenic GFs activate cyclin D and cdk4/6 kinase.

AFTER the restriction point the cells activate the cyclin E and cdk2 kinases meaning the cell will progress to S phase.

in S phase: cyclin A
cdk2 and 3
cdc2
are all activated

in the G2 phase the cyclin B and cdc2 kinases ensure the progression of the cell cycle to mitosis.

26
Q

before the restriction point which kinases are involved?

A

cyclin D and CDK4 and 6 kinases

27
Q

after restriction point which kinases are involved?

A

cyclin E and cdk2

which ensure progression to S phase

28
Q

S phase kinases involved?

A

cyclin A
cdk2 and 3
csc2

29
Q

In. the G2 phase what kinases are involved? what do they do?

A

cyclin B
cdc2 kinases

ensure progression to mitosis

30
Q

how are cyclin/ cdks regulated?

A

at the transcriptional level so specific transcription factors stimulate their expression at the right times

31
Q

what happens to kinases after their role in the cell cycle is complete?

A

targeted by proteases and degraded

32
Q

what occurs at cell cycle checkpoints?

A

DNA damage or defect in spindle formation are detected and this arrests the cycle

33
Q

what happens in cell cycle arrest due to checkpoints?

A

time for the damage to be repaired

if beyond repair, the cell induces the programmed cell death pathway.

34
Q

what happens if the cell cycle isn’t arrested and the cell can replicate with damage?

A

genome instability

35
Q

which cyclins and cdks induce phosphorylation of pRb? effects what?

A

cyclin D
cdk4 or 6

dissociates from E2F and leads to E2F transcriptional activity

36
Q

effect of p53 on cell cycle?

A

stimulates p21 expression which inhibits kinase activity of cdks and causes cell cycle arrest

37
Q

what happens in the case that damage is not repairable?

A

p53 activates genes involved in apoptotic signalling= apoptosis

38
Q

normal conditions at the G2/ M phase checkpoint?

A

the cdc25c is phosphorylated by ‘polo link kinase 1’ and dissociates and translocates to the nucleus
the nuclear cdc25c dephosphorylates the cdk1 cyclin B complex and activates signalling progression to mitosis

39
Q

in normal conditions at the G2/M checkpoint:

what is the cdc25c phosphorylated by? what does it then do

A

polo like kinase 1

translocates to the nucleus

40
Q

what does nuclear cdc25c dephosphorylate?

A

the cdk1 cyclin B complex

41
Q

what does cdc25c dephosphorylation of the cdk1 cyclin B complex do?

A

activates signalling progression to mitosis

42
Q

if these is DNA damage what happens at the G1/M checkpoint?

A

entry to M is prevented by maintaining cdk1 in its hyperphosphorylated inactive form in the nucleus.

43
Q

how is the cdc25c removed from the nucleus in DNA damage at the G2/ M checkpoint?

A

activated Chk1 and chk2 phosphorylate the cdc25c which then translocates out of the nucleus

44
Q

how does the translocation of cdc25c out of the nucleus stop G1/M transition?

A

can no longer dephosphorylate the cdk1-cyclinB complex so entry to M phase is blocked

45
Q

regulatory control checkpoints are _____ in cancer. leading to?

A

defective

cell cycle progression of cells carrying mutations

46
Q

5 small molecule inhibitors of CDKs? type 1

A 
staurosporine 
flavopiridol 
butyrolactone 
roscovitine 
olomoucine
47
Q

staurosporine moa

A

inhibition of protein kinases through the prevention of ATP binding to the kinase

48
Q

flavopiridol MOA?

A

cdk inhibitor- strongest inhibitor

49
Q

butyrolactone MOA

A

Selective inhibitor of the cdk;s

inhibits cell cycle progression of the G1/S and G12/M transitions

50
Q

roscovitine MOA

A

inhibits enzyme targets including cdks (2,7,9) which alter growth phase within cell cycle.

51
Q

olomoucine MOA

A

inhibits cdk 1 which promotes G2/M transition

52
Q

3 ways to indirectly inhibit CDKs? (type 2)

A

mimic p21 activity
cyclin D antagonists
proteasome inhibitors

53
Q

what do proteasome inhibitors do?

A

sensitive malignant cells and tumours to proapoptotic effects of chemotherapy and radiation.

Cancer Biology and Therapy (23 decks)

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