Lecture 43: Cell proliferation- Mitotic signals Flashcards

(41 cards)

1
Q

What is the purpose of the cell cycle?

A

To ensure accurate duplication and division of the genome and cellular contents between daughter cells in an orderly and regulated manner.

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2
Q

What are the four main phases of the cell cycle?

A

G1 (growth), S (DNA synthesis), G2 (preparation for mitosis), M (mitosis).

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3
Q

What is the quiescent phase of the cell cycle?

A

G0 phase – a reversible, non-dividing state where cells can exit the cycle in response to environmental signals.

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4
Q

When do most mammalian cells enter G0?

A

From the G1 phase, particularly in mature tissues with low proliferation rates.

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5
Q

What allows cells to re-enter the cell cycle from G0?

A

Mitogenic (growth) signals like EGF, which initiate signaling cascades promoting cyclin/CDK expression.

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6
Q

How does nutrient availability affect cell cycle speed in yeast?

A

In glucose medium: ~1.5h doubling time. In galactose: ~3.5h. Conditions like nutrient type affect cycle speed.

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7
Q

What is the lag phase in yeast culture growth?

A

Initial phase where cells adapt to new conditions without dividing.

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8
Q

What is the exponential phase?

A

Period of rapid cell division at a constant rate, reflecting the cell cycle’s natural speed.

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9
Q

What is the retardation phase?

A

Slowing growth due to accumulation of waste or depletion of nutrients.

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10
Q

What is the stationary phase?

A

Cells stop dividing and can enter quiescence, but may re-enter the cycle if placed in fresh media.

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11
Q

What are cyclins and what is their role?

A

Cyclins are regulatory proteins whose levels fluctuate to drive cell cycle progression by activating CDKs.

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12
Q

What are CDKs?

A

Cyclin-dependent kinases – enzymes that require binding to a cyclin to phosphorylate target proteins for cycle progression.

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13
Q

How do cyclin-CDK complexes drive the cell cycle?

A

They phosphorylate substrates needed to initiate each phase transition (e.g., DNA replication, mitosis).

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14
Q

Name two cyclins involved in G1 progression.

A

Cyclin D and Cyclin E.

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15
Q

Which CDKs pair with G1 cyclins?

A

CDK4, CDK6 (with Cyclin D) and CDK2 (with Cyclin E).

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16
Q

What are G0 cells?

A

Cells that have exited the cycle and are not actively dividing, often differentiated or temporarily inactive.

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17
Q

Name some examples of cells permanently in G0.

A

Eye lens cells, neurons, and some muscle cells.

18
Q

Are G0 cells metabolically inactive?

A

No. They can be active in function (e.g., producing proteins) but not dividing.

19
Q

What is the clinical importance of G0 in wound healing?

A

Fibroblasts re-enter the cycle from G0 to repair tissue.

20
Q

How is the immune system linked to G0?

A

Lymphocytes in G0 can be activated to divide rapidly during immune responses.

21
Q

What is a mitogen?

A

A signal (e.g., growth factor like EGF) that stimulates cell cycle re-entry from G0.

22
Q

Where do growth signals begin?

A

At the plasma membrane via binding of ligands (e.g. EGF) to receptors (e.g. EGFR).

23
Q

What happens when EGFR binds EGF?

A

Receptor dimerises, autophosphorylates, and activates intracellular signaling cascades.

24
Q

What is Ras and what does it do?

A

A membrane-bound GTPase recruited by adaptor proteins to initiate MAPK cascade.

25
What happens after Ras is activated?
It recruits and activates Raf, starting a kinase cascade ending with MAPK activation.
26
What does MAPK do in mitogenic signaling?
A: Translocates to the nucleus to induce expression of early response genes (e.g., c-Fos, c-Jun).
27
27. Q: How fast are early response genes expressed?
A: Within minutes of growth factor binding.
28
28. Q: What do c-Fos and c-Jun do?
A: Act as transcription factors to activate delayed response genes like G1 cyclins and CDKs.
29
29. Q: What nuclear import pathway helps MAPK enter the nucleus?
A: Importins via nuclear pore complexes (linked to nuclear transport, Lecture 38).
30
30. Q: What is the biological significance of this pathway?
A: Converts external signals into internal gene expression changes, committing cells to division.
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31. Q: What is the restriction point?
A: A checkpoint in late G1 after which the cell is committed to completing the cycle.
32
32. Q: When does the restriction point occur after mitogenic stimulation?
A: About 14–16 hours after the signal is received.
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33. Q: What happens ~6–8 hours after the restriction point?
A: Cells enter S phase and start DNA synthesis.
34
34. Q: How do cancer cells escape cycle control?
A: Through mutations in signaling proteins (e.g. EGFR, Ras, Raf) causing unchecked proliferation.
35
35. Q: How does radiotherapy work?
A: Targets rapidly dividing cells; less effective on G0-phase cells.
36
36. Q: How does chemotherapy work?
A: Attacks actively dividing cells; some drugs target specific phases (e.g., S phase via toxic nucleotides).
37
37. Q: Why are G0 cancer cells problematic in therapy?
A: They're resistant to both radiotherapy and chemotherapy due to lack of proliferation.
38
38. Q: What happens if G0 cancer cells re-enter the cycle?
A: They can repopulate tumors and cause relapse.
39
39. Q: What viral proteins mimic early response genes?
A: v-Fos and v-Jun from sarcoma viruses mimic c-Fos and c-Jun, driving uncontrolled proliferation.
40
40. Q: What percentage of melanomas have Raf mutations?
A: ~66% have mutated, constitutively active Raf, leading to continuous MAPK signaling.
41