Lecture 44: Cell proliferation checkpoints and cell death - Trophic signals

Question 1

4. Q: What molecules regulate the cell cycle?

Answer 1

A: Cyclins and cyclin-dependent kinases (CDKs) regulate progression through the cycle.

Question 2

5. Q: How do growth factors affect the cell cycle?

Answer 2

A: They stimulate G1 cyclins and CDKs, promoting re-entry from G0 to G1.

Question 3

6. Q: What are cell cycle checkpoints?

Answer 3

A: Control mechanisms that ensure DNA integrity before progressing to the next phase.

Question 4

7. Q: Where are the main cell cycle checkpoints located?

Answer 4

A: G1 (restriction point), G2/M checkpoint, and the spindle checkpoint during M phase.

Question 5

8. Q: What is the function of the restriction point in G1?

Answer 5

A: It assesses environmental conditions and DNA integrity before DNA replication.

Question 6

9. Q: Which tumor suppressor protein regulates the G1 checkpoint?

Answer 6

A: Retinoblastoma protein (pRb), encoded by the RB gene.

Question 7

10. Q: How does pRb work?

Answer 7

A: pRb binds and inhibits E2F transcription factors, preventing S phase gene expression until phosphorylated by cyclin D-CDK4/6.

Question 8

11. Q: What is the role of p53 in the cell cycle?

Answer 8

A: p53 senses DNA damage and can trigger cell cycle arrest or apoptosis.

Question 9

12. Q: How is p53 activated?

Answer 9

A: Through post-translational modifications (e.g., phosphorylation) upon DNA damage or cellular stress.

Question 10

13. Q: What genes does p53 activate?

Answer 10

A: Genes that encode CDK inhibitors, which block cyclin/CDK complexes.

Question 11

14. Q: What is Li-Fraumeni syndrome?

Answer 11

A: A condition where individuals inherit one functional TP53 gene copy and are predisposed to early cancers.

Question 12

15. Q: What percentage of human cancers involve p53 mutations?

Answer 12

A: Around 50%.

Question 13

16. Q: What is retinoblastoma?

Answer 13

A: A childhood eye cancer caused by mutations in the RB tumor suppressor gene.

Question 14

17. Q: What’s the difference between hereditary and sporadic retinoblastoma?

Answer 14

A: Hereditary involves one inherited mutant RB allele and one somatic mutation (often affects both eyes), while sporadic involves two somatic mutations (usually one eye).

Question 15

18. Q: What happens in the absence of functional pRb?

Answer 15

A: Retinal cells proliferate uncontrollably, leading to retinoblastoma.

Question 16

19. Q: What phase transition does pRb regulate?

Answer 16

A: G1 to S phase.

Question 17

20. Q: Which CDK/cyclin complexes phosphorylate pRb?

Answer 17

A: Cyclin D-CDK4/6 and cyclin E-CDK2.

Question 18

21. Q: What is apoptosis?

Answer 18

A: Programmed cell death — orderly and non-inflammatory.

Question 19

22. Q: What is necrosis?

Answer 19

A: Uncontrolled cell death — inflammatory and damaging to nearby cells.

Question 20

23. Q: What triggers apoptosis internally?

Answer 20

A: Irreparable DNA damage, lack of trophic signals, and stress like hypoxia.

Question 21

24. Q: What triggers apoptosis externally?

Answer 21

A: Signals from immune cells recognizing infected or damaged cells.

Question 22

25. Q: What are key morphological features of apoptosis?

Answer 22

A: Cell shrinkage, chromatin condensation, nuclear fragmentation, apoptotic bodies, and phagocytosis.

Question 23

26. Q: What proteins mediate apoptosis?

Answer 23

A: Caspases — proteases that cleave cellular components.

Question 24

27. Q: What is a procaspase?

Answer 24

A: An inactive precursor of a caspase that becomes active upon cleavage.

Question 25

28. Q: What keeps caspases inactive in healthy cells?

Answer 25

A: Trophic survival signals from neighboring cells.

Question 26

29. Q: What does CED-3 do in C. elegans?

Answer 26

A: Triggers apoptosis — its mutation causes all 1090 somatic cells to survive.

Question 27

30. Q: What does CED-9 do in C. elegans?

Answer 27

A: Inhibits apoptosis — its mutation causes all 1090 somatic cells to die.

Question 28

31. Q: How does HPV cause cervical cancer?

Answer 28

A: Its E6 protein inhibits p53, and E7 inhibits pRb, removing cell cycle control.

Question 29

32. Q: What cell line originates from HPV-driven cervical cancer?

Answer 29

A: HeLa cells.

Question 30

33. Q: Why are HeLa cells genetically unstable?

Answer 30

A: Due to constant cell cycling and accumulated mutations.

Question 31

34. Q: What happens if DNA repair is active during mitosis?

Answer 31

A: Telomeres can be mistaken as damage, causing chromosome fusion.

Question 32

35. Q: Why must repair mechanisms be turned off during mitosis?

Answer 32

A: To prevent catastrophic chromosomal fusions and misrepair.

Question 33

36. Q: What organism gave insight into apoptosis?

Answer 33

A: Caenorhabditis elegans (C. elegans).

Question 34

37. Q: How many somatic cells die by apoptosis during C. elegans development?

Answer 34

A: 131 out of 1090.

Question 35

38. Q: What developmental processes involve apoptosis in humans?

Answer 35

A: Removal of webbing between fingers and excess neurons during development.

Question 36

39. Q: Why is apoptosis considered the default state?

Answer 36

A: Cells require continuous survival signals to prevent it.

Question 37

40. Q: What does the p53-pRb axis ultimately decide in the cell?

Answer 37

A: Whether to proceed with the cell cycle, repair DNA, or undergo apoptosis.