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Disease, diagnostics and therapeutics > Cell Cycle > Flashcards

Cell Cycle Flashcards

1
Q

what is known as stage G0

A

the quinescent stage

- when the cell isn’t dividing- part of GI

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2
Q

which signal cascades occur during preparation for divisions

A

JAK/STAT, MAPK, P13K, Src

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3
Q

what do JAK/STAT, MAPK, P13K, Src signaling before division cause

A

transcription of Cyclin D and CDK 4/6

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4
Q

in order to pass via any checkpoint you need

A

both cyclins and CDKs

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5
Q

activation of cyclin D occurs especially via

A

Wnt and MAPK

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6
Q

Activation of cyclin D via Wnt

A

1) Wnt binds to frizzled
2) APC/axin and GSK3beta (kinase) i complex
3) dishevelled binds to APC- activating APCs inhibition GSKbeta
4) therefore GSKbeta doesn’t phosphorylate Beta-Catedin
5) Beta-Catedin (TF) translocates to the nucleus where it transcribes cyclin D and CDK4/6

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7
Q

activation of cyclin D viaMAPK

A
  1. EGF/ mitogen bind to TK
  2. Trans- Autophosphorylation
  3. Recruiting Grb2/SOS
  4. Activated SOS bind to RAS (small GTP) and activates by phosphorylation
  5. RAS- RAF-MEK-ERK
  6. ERK= TF
  7. Produces cyclin D and CDK4/6 produced
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8
Q

role of Cyclin D/ CDK 4/6

A

transitions the cell to G1 out of G0 and also used at the G1/s checkpoint

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9
Q

only the the concentration of Cyclin D and CDK4/6 reaches a threshold

A

can the cell cycle progress

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10
Q

what occurs during G1

A

cell synthesises mRNA and proteins to prepare for organelle and DNA replication

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11
Q

absence of int and p53

A

will stop cyclin D and CDK4/6 being produced- therefore no cell cycle profression

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12
Q

what causes absence of p53

A

p21/p27

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13
Q

relationship between cyclins and CDKs

A

cyclins and CDK (kinase) complex, when cyclins binds to CDK they are change conformational (partially activated). Become fully active by phosphorylation by CAK (CDK activating kinase

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14
Q

what fully activates cyclins and CDK complexes

A

CAS- CDK activating eznyme

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15
Q

what CDKs and cyclins are produced during G1/S

A

cyclin D and cyclin E and CDK 4, 6, 2

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16
Q

which pathway used in G1/s

A

RB/E2F

a) Activated cyclinD and CDK complex causes RB to release E2F
b) E2F can translocate to the nucleus and cause transcription of the next cyclin Cyclin E and CDK2
c) CDk2 and cyclin E complex

17
Q

when cell damage has occurred and mitosis needs to be stopped

A

-p21/p27 block the association of cyclin/cdk complexes
they block the phosphorylation of the complexes by blocking CAK (steric hinderence)
e.g. P21/P27 preventing Cyclin D/CDK4/6 from activating RBand therefor eRB/ E2F do not dissociated and E2F cannot translocate to the nucleus and can cause transcription of Cyclin E and CDK2

18
Q

p53 pathways transcribes

A

p21/p27

19
Q

P53 pathway

A

P53 which transcribed P21/P27

  • Activated during DNA damage
    a) During cell damage ATM kinase activated
    b) This phosphorylates Chk kinase ½ which causes P53 to dislocates from MDM2
    c) P53 transolcates to the nucleus and repairs DNA and also transcribes P21/P27
20
Q

how to P21 and P27 stop mitosis

A

e.g. P21/P27 preventing Cyclin D/CDK4/6 from activating RB and therefor eRB/ E2F do not dissociated and E2F cannot translocate to the nucleus and can cause transcription of Cyclin E and CDK2

21
Q

S1 phase

A
  • Cyclin A resides in the nucleus and associates with CDK2
  • When the quantity of cyclinA/CDK2 complex reaches the threshold value it inhibits cyclin E
  • This suppresses previous cycles i.e. the cell cycle can progress and not start another cycle
22
Q

cyclins in S1 phase

A

cyclin A and CDK 2

23
Q

G2 phase

A

Cells checks for faithful replication of DNA
Produces proteins needed for cell division
- Cyclin B complexes with CDK2 (suppressed by p21, p27)
- Cyclin B causes transcription of proteins important in spindle formation e.g. microtubules

24
Q

cyclins ing G2

A

cyclin B and CDK2 - transcription of microtubules for spindle formation

25
Q

G2/M checkpoint

A

In a normal cell:

a) Wee1 is phosphorylated
b) Meaning it can be tagged with ubiquitin (E1, E2, E3 ubiquitin ligase)
c) Sent to proteasome for degradation
d) Cyclin B then complexes with other proteins which allows transition through G2/M checkpoint

26
Q

metaphase

A
  • Centrioles migrate to the piles
  • Radiate spindle (microtubule)
  • Spindle fibre binds to cohesion preventing premature chromosome separation)
27
Q

what is important in metaphase

A

that all chromosomes are attached to spindles at the kinetochore

28
Q

how does the cell check all spindle fibre are bound to the kinetochore

A
  • Spindle fibre binds to cohesion preventing premature chromosome separation
  • P31 is released from cohesion when all spindle fibres are bind to kinetochore
  • Causing APC to bind to securing/seperase
  • Seperase binds to cohesion and allows spindles to contract and pull chromosomes apart
29
Q

mitochondria

A
30
Q

H2O2 inhibits pathways such as

A

MAPK, P53 stopping initiation of cell cycle

31
Q

p53 causes the transcription of

A

p21/ p27

32
Q

p21/p27

A

produced due to p53 transcribing them

- stop cell cycle progression by inhibiting CAK

Disease, diagnostics and therapeutics (53 decks)

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