Mechanisms of disease Flashcards

1
Q

How can the cell cycle be visualised/quantified?

A

visualised via fluorescence microscopy which generates stains of proteins.

quantified via fluorescent flow cytometry which measures the DNA content of every cell population

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How is the cell cycle regulated?

A

Regulated via cyclin-dependent kinases (CDK) which form a complex with cyclin, causing its activation. It then phosphorylates a specific substrate protein.

This is regulated by:

  1. continuous cycles of synthesis/apoptosis
  2. post-translational modification via phosph.
  3. dephosphorylation
  4. binding of CDKI
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are cyclins?

A

encoded by 20 genes, cyclins are regulatory subunits controlled by GF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are CDKs?

A

encoded by 10 genes, CDKs are catalytic subunit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Explain the mechanism of retinoblastoma protein .

A

1/ unphosphorylated Rb binds to E2F transcription factors, preventing expression of S-phase proteins
2/ in presence of cyclin D-CDK4 or cyclin E-CKD2, Rb becomes phosphorylated and drives replication. It also stimulates expression of more cyclin E, creating a positive feedback.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Explain the regulation of cell cycle and apoptosis.

A
  1. GF drive early gene expression - TF FOS, JUN, MYC
  2. This stimulates delayed gene expression
  3. E2F sequestered by binding to unphosphorylated RB
  4. G1 cyclin-CDK complexes hypophosphorylate Rb allowing more E2F activity + more cyclin E, S-phase proteins
  5. G1/S phase cyclin-CDK complexes hyperphosphorylate Rb - stimulating release of E2F

Switches activated by post-translational modification or removal of inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Explain mechanisms by which growth control can be disrupted in neoplasia

A

TP53 is continually destroyed by proteasome.

Mutagen binding induce activation of protein kinases which phosphorylate TP53 preventing its destruction to:

  1. drive expression of CDK (malfx: cells proliferate faster)
  2. activates DNA repair mechanism (malfx: more mutations)
  3. induce apoptosis (malfx: become resistant to dying)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Define drugs acting on the cell cycle: S-phase drugs

A

they cause DNA damage

  1. 5-fluorouracil - prevent thymidine synthesis
  2. cisplatin - binds to DNA to cause damage and block repair
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Define drugs acting on the cell cycle: M-phase drugs

A
they target the mitotic spindle:
vinca alkaloids, paclitaxel :
- stabilises microtubules
- prevent polymerisation
- arrest cells in mitosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Define the response of the cell in response to DNA damage

A

may trigger cell cycle arrest or apoptosis:

  1. stop the cell cycle - CDKI genes, CHEK2, etc.
  2. DNA repair - nucleotide/base excision enzymes, mismatch repair, etc.
  3. programmed cell death - BLC family, caspases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly