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NTC > Week 2 The Nucleus and Cell Cycle Questions > Flashcards

Week 2 The Nucleus and Cell Cycle Questions Flashcards

1
Q

What is the role of Cyclin-Dependent Kinases (CDKs) in the regulation of the cell cycle?

A
  • They can phosphorylate downstream proteins only when when bound to their cyclin partner
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2
Q

What is the G1 Cyclin-CDK complex?

A

Cyclin D with CDK4 or CDK6

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3
Q

What is the G1/S Cyclin-CDK complex?

A

Cyclin E with CDK2

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4
Q

What is the S Cyclin-CDK complex?

A

Cyclin A with CDK2 or CDK1

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5
Q

What is the m Cyclin-CDK complex?

A

Cyclin B with CDK1

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6
Q

How are CDKs activated?

A

Cyclin binds to CDK. CDK-activating kinase (CAK) binds to this complex.

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7
Q

What is the role of Wee1 Kinase in the regulation of the cell cycle?

A

It can inhibit activated CDKs by inhibitory phosphorylation.
It adds 2 phosphates

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8
Q

What is the role of Cdc25 in the regulation of the cell cycle?

A

It is a photphatase enzyme that removes inhibitory phosphates, reactivating the Cyclin-CDK complex.

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9
Q

What is the role of Protein Phosphatase 2A (PP2A-B53) in regulation of M-CDK activity?

A
  • De-phosphorylates protein targets that CDK has phosphorylated.
  • This halts cell cycle progression.
  • PP2A very active during interphase (preventing mitosis at this time).

DURING MITOSIS:
- M-CDK phosphorylates Greatwall Kinase, which, in turn, phosphorylates Enza. Enza binds to PP2A, inhibiting it.

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10
Q

Moving from G1 to S

What are the key advantages of the intracellular braking system?

A
  • Ensures one process doesn’t begin before previous one completed.
  • Allows cell cycle to be regulated by environmental signals.
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11
Q

How is Rb involved in the intracellular braking system, preventing cell going from G1 to S?

A

It binds and inactivates E2F (a transcription factor which upregulates S-phase genes). When it is phosphorylated by Cyclin D-CDK4 complex, it releases E2F, continuing cell cycle.

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12
Q

Name 3 key CDK-Inhibitors and their mechanism of action.

A

P27: suppresses G1/S CDK activity and S-CDK activity in G1 (helps cell withdraw from cell cycle).
P21: suppresses G1/S – CDK and S-CDK activities after DNA damage in G1 (transcriptionally activated by p53).
P16: suppresses G1 CDK (this is Cyclin D, CDK4,6) activity (frequently inactivated in human cancer).

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13
Q

What is a PEST sequence?

A

A segment rich in proline (P), glutamic acid (E), serine (S) and threonine (T) residues.
This sequence allows ubiquitin to bind to the protein, tagging for degradation.
Cyclin D and E contain PEST sequences.

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14
Q

How does the Anaphase Promoting Complex (APC) trigger metaphase to anaphase transition?

A
  • APC is a ubiquitin ligase.
  • It catalyses the degradation of M and S Cyclins.
  • This inactivates the corresponding CDKs.
  • Phosphorylated proteins are dephosphorylated by PP2A and other protein phosphatase enzymes.
  • APC is activated by Cdc20, catalysing degradation of securin and cyclins.
  • This causes separatation of chromosomes in anaphase.
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15
Q

What is the role of SCF in control of the cell cycle?

A
  • Ubiquitylation of CKI proteins in late G1, helping to control the activation of S-Cdks and DNA replication.
  • Destruction of G1/S-cyclins in early S phase.
  • SCF activity is constant during the cell cycle. Ubiquitylation controlled by changes in the phosphorylation state of its target proteins.
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16
Q

P53

How a cell recognise DNA damage and arrest the cell cycle in G1?

A
  • Phosphorylation of P53 in response to DNA damage.
  • Allows P53 to dissociate from MDM2 (a ubiquitin ligase).
  • Active P53 binds to regulatory region of p21 gene.
  • Expression of P21 that binds to and inctivates G1 and S CDK complexes.
17
Q

Give an example of an inhibitory growth factor - how does it work?

A

TGF-Beta, binds to receptor, upregulating CDK inhibitors - mainly P16.

18
Q

How does activation of the M-CDK complex trigger breakdown of the nuclear envelope and chromosome condensation?

M-CDK complex is Cyclin B with CDK1.

A
  • M-CDK complex phosphorylates lamins (intermediate filaments that support nuclear envelope).
  • Causes brekadown of nuclear envelope.
  • M-CDK complex phosphorylates condensins (proteins that support chromosome condensation).

NTC (6 decks)

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