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Cellular pathology > Cellular growth regulation > Flashcards

Cellular growth regulation Flashcards

1
Q

What are proteins that stimulate proliferation called?

A

Proteins that stimulate proliferation are called mitogens

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2
Q

What are mitogens usually named after?

A

Usually named after originally identified target

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3
Q

What types of proteins are there in the cell cycle

A
  • Their are proteins that stimulate differentiation and inhibit proliferation like TGFbeta
  • Their are proteins that induce apoptosis like TNFalpha and other members of the TNF family
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4
Q

What are the 3 broad classes of proteins?

A
  • Paracrine: which are produced locally to stimulate proliferation of a different cell type that has the appropriate cell surface receptor
    • Autocrine: which are produced by a cell that also expresses the appropriate cell surface receptor
    • Endocrine: which like conventional hormones, is released systemically for distant effects
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5
Q

What are the phases of the

A

M phase
G1 phase
S phase
G2 phase

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6
Q

What happens in the m phase of the cell cycle?

A

M phase is the seperation of chromosomes and divison into 2 daughter cells

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7
Q

What happens to the 2 daughter cells after mitosis?

A

1 cell used in interphase for cell growth(G1) as well as DNA replication(S Phase)

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8
Q

What do the cells do in the G2 phase?

A

In the G2 phase, cells prepare for mitosis

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9
Q

What happens after cell division?

A

After cell division, cells have 2 copies of each chromosome. In G1 we have 2 copies and after G2 we have 4 copies

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10
Q

What is the way to check whether cells are growing fast?

A
  • Fluorescence activated cell sorter analysis of cell DNA content
    • We take cells and label DNA with dye and use laser to see intensity of cells
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11
Q

DNA replication steps

A
  1. DNA is replicated semi-conservatively
  2. New DNA is synthesised in the 5’to3’ direction from the deoxynucleotide triphosphate precursors at a replication fork by a multienzyme complex
  3. Fidelity is determined by base pairing and presence of a proof reading enzyme in DNA polymerase
  4. Synthesis of the new DNA strand uses an RNA primer and occurs continuously on the leading strand and discontinuously on the trailing strand(giving rise to okazaki fragments, which are ligated together after the removal of the RNA primer)
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12
Q

What are the stages of mitosis?

A
  1. Prophase
  2. 5Propmetaphase
  3. Metaphase
  4. Anaphase
  5. Telophase
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13
Q

Steps in prophase

A
  • Nucleus become less definite
  • Microtubular spindle apparatus assembles
  • Centrioles migrate to poles
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14
Q

Steps in prometaphase

A
  • Nuclear membrane breaks down

- Kinetochores attach to spindle in nuclear regions

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15
Q

Steps in metaphase

A

Chromosomes align in equatorial plane

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16
Q

Steps in anaphase

A

Chromatids separate and migrate to opposite poles

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17
Q

Steps in telophase

A

Daughter nuclei form

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18
Q

What happens in cytokinesis?

A
  • Division of cytoplasm

- Chromosomes decondense

19
Q

Examples of S phase active drugs

A

5-Fluorouracil

Bromodeoxyuridine

20
Q

What is 5-Fluorouracil?

A

5-Fluorouracil is an analogue of thymidine and blocks thymidylate synthesis

21
Q

What is bromodeoxyuridine?

A

Bromodeoxyuridine is another analogue that maybe incorporated into DNA and is detected by antibodies to identify cells that have passed through the S-phase

22
Q

Examples of M phase active drugs

A
  • Colchichine
  • VInca Alkaloids
  • Paclitaxel
23
Q

What does colchicine do?

A

Colchicine stabilizes free tubulin, preventing microtubule polymerization and arresting cells in mitosis and is used in karyotype analysis

24
Q

What are vinca alkaloids similar to?

A

Vinca alkaloids are similar to colchicine

25
Q

What type of drug is paclitaxel?

A

Is a taxol(anticancer drug) which stabilises microtubules and prevents de-polymerization

26
Q

What do cell cycle checkpoint controls ensure?

A

Controls ensure the strict alternation of mitosis and DNA replication

27
Q

What do the restriction point just before the S phase check?

A

They check if DNA is not damaged, cell size and metabolite/nutrients store

28
Q

What phase of the cell cycle are cells responsive to growth factors?

A

Cells are only responsive to growth factors during the G1 phase of the cell cycle

29
Q

What does cyclin dependent kinase activity control?

A

Cyclin dependent kinase activity controls cell cycle progression

30
Q

What do active cyclin-CDK do?

A

Active cyclin-CDK complex phosphorylates specific substrates

31
Q

What processes are in place to regulate cyclin-CDK activity?

A
  • Cyclical synthesis(Gene expression) and destruction(by proteasomes)
  • Post translational modification by phosphorylation- depending on modification site as it may results in activation, inhibition or destruction
  • Dephosphorylation
  • Binding of cyclin dependent kinase inhibitors
32
Q

What is the retinoblastoma protein a key substrate of?

A

The retinoblastoma protein is a key substrate of G1 and G1/S cyclin dependent kinases

33
Q

Retinoblastoma and E2F

A
  • Unphosphorylated RB binds E2F preventing its stimulation of S-phase protein expression
    • Cyclin D or Cyclin E can phosphorylate retinoblastoma meaning retinoblastoma can’t bind to E2f
    • Released E2F stimulates the expression of more cyclin E and S phase proteins like DNA polymerase, thymidine kinase etc. This allows DNA replication to start.
34
Q

What are the 2 families of Cyclin dependent kinase inhibitors

A
  1. CDK inhibitory protein/kinase inhibitory protein family

2. Inhibitor of kinase 4 family

35
Q

What weakly and strongly stimulates the expression of the CDK inhibitory protein/kinase inhibitory protein family

A

-Expression of members of this family stimulated weakly by TGFbeta and strongly by DNA damage

36
Q

What do proteins of the CDK inhibitory protein/kinase inhibitory protein family inhibit?

A

Inhibit all other CDK-cyclin complexes

37
Q

What are proteins of the CDK inhibitory protein/kinase inhibitory protein family gradually sequestered by?

A

Are gradullay sequestered by G1 CDKs this allowing activation of later CDKs

38
Q

What stimulates the expression of inhibitor of kinase 4 family proteins ?

A

Expression stimulated by TGFbeta

39
Q

What do proteins of inhibitor of kinase 4 proteins specifically inhibit?

A

Specifically inhibit G1 CDKs

40
Q

What induces cyclin expression?

A

Growth factors induce cyclin expression

41
Q

How do growth factors induce cyclin expression?

A

-Growth factor bind to growth factor receptor activating signal transducers which stimulates kinase cascade that allows a wave of transcription factor activation forming mRNA and proteins

42
Q

What are the sequence of events triggered by growth factors?

A

-Growth factors signalling activates early gene expression(transcription factors)
-Early gene products stimulate delayed gene expression
-E2f sequestered by binding to unphosphorylated retinoblastoma protein
-G1 cyclin-CDK complexes hypophosphorylate retinoblastoma and then G1/S cyclin-CDK complexes hyperphosphorylate retinoblastoma releasing E2F
-E2F stimulates expression of more cyclin E and S-phase proteins
S phase cyclin-CDK and G2/M cyclin-CDK complexes build up in inactive forms. These switches are activated by post translational modification or removal of inhibitors, driving the cell through S-phase and mitosis

43
Q

When is DNA damage detected and what’s triggered?

A

DNA damage is detected at checkpoints triggering cell cycle arrest or apoptosis

44
Q

What are the 3 steps that happen when DNA damage is detected?

A
  1. Cycle stopped
  2. DNA repair is attempted
  3. Programmed cell death if repair impossible

Cellular pathology (12 decks)

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