Exam 18: Cell Death

Which of the following morphological changes is NOT typically seen in a cell that is undergoing apoptosis?

Soon after the discovery of nerve growth factor (NGF), researchers injected newborn mice with rabbit antiserum (i.e. serum that contains antibodies) against NGF. They observed massive nerve cell death compared to appropriate control injections. Up to 99% of the neurons in some parts of the developing peripheral nervous system died after about a week of daily injections. These results suggest that ...

Indicate whether each of the following mutations would likely promote (P) or inhibit (I) apoptosis in cells harboring the mutation(s). Your answer would be a four-letter string composed of letters P and I only, e.g. PPPI. ( ) Mutations in the pro-apoptotic effector Bcl2 family proteins Bax and Bak that prevent their association with the outer mitochondrial membrane. ( ) A mutation in the BIR domain of the IAP protein DIAP1 that prevents binding to either caspases or anti-IAP proteins. ( ) A mutation in the anti-IAP protein Reaper that prevents its binding to the IAP proteins. ( ) A mutation in the CARD domain of caspase-9 that prevents its binding to Apaf1.

Indicate true (T) and false (F) statements below regarding programmed cell death by apoptosis. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF. ( ) Apoptosis is the final fate of almost all cells in an adult animal. ( ) Even perfectly healthy cells may undergo apoptosis. ( ) DNA damage that cannot be repaired inhibits apoptotic pathways. ( ) Apoptosis is the main form of programmed cell death in plant cells as well as in animal cells.

For each of the following proteins that are proteolytically cleaved in apoptosis, indicate whether the cleavage is first carried out by an initiator (I) or executioner (E) caspase. Your answer would be a five-letter string composed of letters I and E only, e.g. EEEII. ( ) The initiator caspase-2 ( ) The executioner caspase-3 ( ) The BH3-only protein Bid ( ) The endonuclease inhibitor iCAD ( ) The nuclear protein Lamin A

The Bcl2 family is comprised of anti-apoptotic (A), BH3-only (B), and effector (E) proteins. In the following diagram representing the regulation of the intrinsic pathway of apoptosis, what class of activated Bcl2 family proteins (A, B, or E) corresponds to boxes 1 to 3, respectively? Your answer would be a three-letter string composed of letters A, B, and E only, e.g. ABE.

Indicate true (T) and false (F) statements below regarding apoptosis in disease. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF. ( ) Either excessive or insufficient apoptosis can contribute to disease. ( ) Excessive apoptosis, in many cases, leads to autoimmune disease and cancer. ( ) In about half of human cancers, the tumor suppressor protein p53 is mutated. ( ) Drugs that interfere with the function of Bcl2 family proteins such as Bax and Bak may treat cancers by stimulating apoptosis.

Apoptotic cells are efficiently phagocytosed by neighboring cells or macrophages. Which of the following DOES NOT normally happen in this process?

Initiator and executioner caspases share all of the following features EXCEPT that ...

Fill in the blank: In the intrinsic pathway of apoptosis, a protein called ... is released from the mitochondria into the cytosol and binds to the adaptor protein Apaf1, causing it to oligomerize into a wheel-like assembly called an apoptosome, which then recruits initiator caspase-9 proteins.

v-FLIPs are viral proteins that were first identified as modulators of apoptosis; they contain two death effector domains, which are also found in some initiator caspases such as procaspase-8. These v-FLIP proteins can be recruited to the DISC through the binding of the death effector domain to similar domains in the adaptor proteins, but are otherwise catalytically inactive. What do you think is the effect of v-FLIP expression in the host cell?

Which of the following proteins activates the mitochondrial pathway of apoptosis?