Lecture 44: Cell proliferation checkpoints and cell death - Trophic signals Flashcards
- Q: What molecules regulate the cell cycle?
A: Cyclins and cyclin-dependent kinases (CDKs) regulate progression through the cycle.
- Q: How do growth factors affect the cell cycle?
A: They stimulate G1 cyclins and CDKs, promoting re-entry from G0 to G1.
- Q: What are cell cycle checkpoints?
A: Control mechanisms that ensure DNA integrity before progressing to the next phase.
- Q: Where are the main cell cycle checkpoints located?
A: G1 (restriction point), G2/M checkpoint, and the spindle checkpoint during M phase.
- Q: What is the function of the restriction point in G1?
A: It assesses environmental conditions and DNA integrity before DNA replication.
- Q: Which tumor suppressor protein regulates the G1 checkpoint?
A: Retinoblastoma protein (pRb), encoded by the RB gene.
- Q: How does pRb work?
A: pRb binds and inhibits E2F transcription factors, preventing S phase gene expression until phosphorylated by cyclin D-CDK4/6.
- Q: What is the role of p53 in the cell cycle?
A: p53 senses DNA damage and can trigger cell cycle arrest or apoptosis.
- Q: How is p53 activated?
A: Through post-translational modifications (e.g., phosphorylation) upon DNA damage or cellular stress.
- Q: What genes does p53 activate?
A: Genes that encode CDK inhibitors, which block cyclin/CDK complexes.
- Q: What is Li-Fraumeni syndrome?
A: A condition where individuals inherit one functional TP53 gene copy and are predisposed to early cancers.
- Q: What percentage of human cancers involve p53 mutations?
A: Around 50%.
- Q: What is retinoblastoma?
A: A childhood eye cancer caused by mutations in the RB tumor suppressor gene.
- Q: What’s the difference between hereditary and sporadic retinoblastoma?
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).
- Q: What happens in the absence of functional pRb?
A: Retinal cells proliferate uncontrollably, leading to retinoblastoma.
- Q: What phase transition does pRb regulate?
A: G1 to S phase.
- Q: Which CDK/cyclin complexes phosphorylate pRb?
A: Cyclin D-CDK4/6 and cyclin E-CDK2.
- Q: What is apoptosis?
A: Programmed cell death — orderly and non-inflammatory.
- Q: What is necrosis?
A: Uncontrolled cell death — inflammatory and damaging to nearby cells.
- Q: What triggers apoptosis internally?
A: Irreparable DNA damage, lack of trophic signals, and stress like hypoxia.
- Q: What triggers apoptosis externally?
A: Signals from immune cells recognizing infected or damaged cells.
- Q: What are key morphological features of apoptosis?
A: Cell shrinkage, chromatin condensation, nuclear fragmentation, apoptotic bodies, and phagocytosis.
- Q: What proteins mediate apoptosis?
A: Caspases — proteases that cleave cellular components.
- Q: What is a procaspase?
A: An inactive precursor of a caspase that becomes active upon cleavage.
- Q: What keeps caspases inactive in healthy cells?
A: Trophic survival signals from neighboring cells.
- Q: What does CED-3 do in C. elegans?
A: Triggers apoptosis — its mutation causes all 1090 somatic cells to survive.
- Q: What does CED-9 do in C. elegans?
A: Inhibits apoptosis — its mutation causes all 1090 somatic cells to die.
- Q: How does HPV cause cervical cancer?
A: Its E6 protein inhibits p53, and E7 inhibits pRb, removing cell cycle control.
- Q: What cell line originates from HPV-driven cervical cancer?
A: HeLa cells.
- Q: Why are HeLa cells genetically unstable?
A: Due to constant cell cycling and accumulated mutations.
- Q: What happens if DNA repair is active during mitosis?
A: Telomeres can be mistaken as damage, causing chromosome fusion.
- Q: Why must repair mechanisms be turned off during mitosis?
A: To prevent catastrophic chromosomal fusions and misrepair.
- Q: What organism gave insight into apoptosis?
A: Caenorhabditis elegans (C. elegans).
- Q: How many somatic cells die by apoptosis during C. elegans development?
A: 131 out of 1090.
- Q: What developmental processes involve apoptosis in humans?
A: Removal of webbing between fingers and excess neurons during development.
- Q: Why is apoptosis considered the default state?
A: Cells require continuous survival signals to prevent it.
- Q: What does the p53-pRb axis ultimately decide in the cell?
A: Whether to proceed with the cell cycle, repair DNA, or undergo apoptosis.
