EXAM III Final Flashcards
What are two cell phenotypes that cause them to undergo apoptosis?
- Macrophage activation
- DNA fragmentation
- A decrease in the nucleus and volume
- Less adhesion, smaller cytoskeleton and nuclear envelope
Explain the difference between initiator and executioner caspase
Initiator caspase (-8,9) initiates apoptosis by activating the caspase cascade by causing executioner caspase (-3) to actually cleave the downstream targets. (Such as cytoskeleton, inactive endonuclease, proteins, cell adhesion proteins)
Executioner caspase executes apoptosis
Name two ways in which proto-oncogenes become activated to become oncogenes
- Gene amplification, which causes the overproduction of a normal protein.
- Chromosome rearrangement by a nearby regulatory DNA sequence that brings new regulatory sequence that causes overproduction of a normal protein or Creates overactive fusion protein. (I.e. EGF receptor rearrangement can remove the extracellular domain; epidermal growth factor)
- Regulatory mutation which causes an overproduction of a normal protein. (I.e. Promoter mutation)
- Deletion or point mutation in a coding sequence causing a hyperactive protein in normal amounts (I.e. Ras)
Describe the pathology of cancer and how it goes from benign to malignant
A tumor is originally benign. Once it invades a nearby capillary the tumor has become malignant and is capable of entering tissues via the blood vessels. Tumors can also become adhered to the endothelial vessel walls.
Describe polyp and how it develops
A polyp is a precursor to colorectal cancer (APC tumor suppressor gene mutation). They normally take about ten years to develop and if left untreated can become malignant and be cancerous. If the polyp is excised, the patient is cured.
Explain how Gleevec is used in the treatment of anti-cancer therapy
Gleevec is used in chronic myeloid nous leukemia (via Philadelphia chromosome translocation) and binds to the ATP binding site of BCR/Abl, inhibiting tyrosine kinase activity thereby inhibiting cell proliferation
What are the two forms of cell death?
- Necrosis - contents spill out
2. Apoptosis - cell death under physiological conditions (programmed; cells shrink and condense)
T/F; Eliminating lymphocytes after destroying and ingesting microbes is an example of apoptosis
True
T/F; programmed cell death is important for certain cells such as those that are abnormal, non-functional, or potentially dangerous
T
T/F; cytochrome c is a marker of apoptosis
True; released from mitochondria
T/F; apoptosis is an extracellular proteolytic cascade mediated by caspases (proteases)
False; apoptosis is intracellular
T/F; Cysteine is the active site on caspases
True; Cysteine aspartyl specific proteins
T/F; Caspases targets proteins and cleaves them in their sequence where a glycine amino acid residue occurs
False; cleaves where there’s an Aspartic amino acid residue
T/F; pro caspase is an inactive precursor of caspase
True; this is the primary synthesized version of caspase
T/F; the active form of caspase is a heterodimer
True; made up of large and small subunits which forms the heterodimer
T/F; the caspase cascade is reversible
False; it’s actually irreversible
Are death receptors involved in the intrinsic or extrinsic pathway of apoptosis?
Extrinsic
Intrinsic involves cytochrome c from mitochondria
Explain how decoy receptors work in the extrinsic pathway of apoptosis
Decoy receptors contain ligand binding domain (no death domains) which blocks the binding of Fas ligand to the Fas death receptor
Explain how the protein FLIP works in the extrinsic pathway of apoptosis
FLIP is a competitive inhibitor to pro caspase-8,10 death effector domain, thereby inhibiting apoptosis
What are some factors that cause activation of the intrinsic pathway of apoptosis?
Injury
DNA damage
Lack of oxygen, nutrients
Lack of extracellular survival signals
What is the function of cytochrome c in the intrinsic pathway of apoptosis?
Released from intermediate space of mitochondria and binds to adaptor protein to activate procaspases
Define Apaf1
Apoptotic protease activating factor-1; bound by cytochrome c which becomes an apoptosome and activates caspase-9 (initiator caspase_
What are the two types of Bcl2 proteins that control the release of cytochrome c into the Cytosol?
Pro-apoptotic = BH3 and BH123 (Bax, Bak)
Anti-apoptotic = Bcl2 (Bcl-XL, BH1234) = located on cytosolic surface and prevents the aggregation of BH123 (active form)
What is the mechanism of BH3 in the intrinsic pathway of apoptosis?
Pro-apoptotic and located in Cytosol and inhibits anti-apoptotic Bcl2 protein from inhibiting aggregation of BH123 for the release of cytochrome c