checkpoints Flashcards

1
Q

what mediates Rb hypophosphorylation?

A

cyclin D/cdk4/6 complex

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2
Q

what mediates Rb hyperphosphorylation?

A

cyclin E/cdk2 complex

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3
Q

describe the role of E2Fs in mediating cell cycle progression?

A

during early-mid g1 - unphosphorylated or hypophosphorylated Rb binds E2Fs + blocks its transcriptional activity
during r point - hyperphosphorylated Rb releases E2Fs from complex + E2Fs transcribe target genes mediating g1/s transition
E2F target gene = cyclin E -> E2Fs drive their own activation

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4
Q

how is E2F activity short lived?

A

as cell undergoes g1/s transition cyclin A/cdk2 complex inhibits E2Fs - targets E2Fs for degradation via ubiquitination

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5
Q

describe how cells progress to anaphase when chromosomes are aligned

A

APC/C activated
cohesin holds 2 sister chromatids together
APC/C ubiquitinates securin -> targets securin for proteosomal degradation
separase is held in a complex with securin = inactivates separase
when securin is degraded, separase = active
separase degrades cohesin so 2 sister chromatids can separate

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6
Q

what is MPF = maturation promoting factor also known as?

A

M-phase promoting factor

cyclin B/CDC2 complex

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7
Q

what is cell cycle arrest mediated by?

A

ATM

ATR

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8
Q

p53

A

tumour suppressor
transcription factor promoting expression of genes promoting growth suppression, apoptosis and DNA repair
target gene = p21cip1 = cdk inhibitor –> prevents cell cycle progression

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9
Q

DEFINE: anoikis

A

cell detachment induced apoptosis

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10
Q

myc-max complex

A

promotes proliferation

inhibits differentiation

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11
Q

mad-max complex

A

promotes differentiation

inhibits proliferation

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12
Q

what are the actions of the myc/max complex on the cell cycle clock?

A
  • promotes cyclin D2/cdk4 complexes
  • promotes E2F transcription factors
  • promotes myc/miz1
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13
Q

what is the role of myc/miz1

A
  • suppresses transcription of ckis so liberates cyclin D2/cdk4 & cyclin E/cdk2 complexes from inhibition
  • promotes degradation of p27kip1
    allows progression through r point
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14
Q

describe an experiment showing that myc activation alone is sufficient to relieve all constraints on proliferation

A

ectopically expressed myc as a fusion protein by attaching myc to an oestrogen receptor
no ligand? -> myc is sequestered in cytoplasm = inhibited
oestrogen or tamoxifen added? -> change in conformation of complex driving myc translocation to nucleus as a TF = active
when oestrogen or tamoxifen was added during G0 in absence of growth factors, myc was active enough to drive entry into g1 and s phase

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15
Q

what are some cancer cell strategies used to oppose TGFβ signalling?

A
  • mutant Smad = inactivates smad
  • mutant TGFβ receptor = inactivated
  • deregulate pRb pathway by:
  • mutate pRb = inactivates pRb
  • very high expression levels of cyclin D1 - hypophosphorylates Rb
  • downregulate INK4 proteins
  • mutate CDK4 so unable to bind CKIs
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16
Q

where do the vast majority of point mutations in p53 occur in?

A

dna binding domain

p53 unable to bind dna + promote transcription of p53 target genes

17
Q

what are some signals inducing p53?

A
damage
stress
* hypoxia 
* UV radiation
* lack of nutrients
18
Q

what regulates p53 levels and how does it do so?

A

mdm2
cell in normal conditions: mdm2 binds p53 and promotes ubiquitination then proteosomal degradation
stress or damage:
1. atm/atr pathways activated
2. leads to activation of chk2
3. phosphorylation of p53
* phosphorylated p53 cannot bind to mdm2 so cannot be ubiquitinated by mdm2
* ATM phosphorylates mdm2 –> inactivating mdm2
mitogenic or cell survival signals present:
1. more mdm2 transcription induced
mdm2 phosphorylated at a different residue - activates mdm2 + facilitates mdm2 binding to p53
2. more p53 ubiquitination and degradation

19
Q

which subunit activates APC/C

A

Cdc20

20
Q

what is the synaptonemal complex

A

protein structure that forms between homologous chromosomes

21
Q

DEFINE: non-disjunction

A

2 homologues not properly separated resulting in gametes with an extra chromosome or lacking a chromosome