Question

Indicate whether each of the following mutations would likely promote or inhibit apoptosis in cells harboring the mutation(s). Explain each answer. a) Mutations in the pro-apoptotic effector Bcl2 family proteins Bax and Bak that prevent their association with the outer mitochondrial membrane. b) A mutation in the BIR domain of the IAP protein DIAP1 that prevents binding to either caspases or anti-IAP proteins. c) A mutation in the anti-IAP protein Reaper that prevents its binding to the IAP proteins. d) A mutation in the CARD domain of caspase-9 that prevents its binding to Apaf1.

Answer 1

Inhibiting Apoptosis:

Mutations in the pro-apoptotic effector Bcl2 family proteins Bax and Bak that prevent their association with the outer mitochondrial membrane

(Bax and Bak induce the release of cytochrome C which induces apoptosis)

A mutation in the anti-IAP protein Reaper that prevents its binding to the IAP proteins

(IAP proteins are inhibitors of the Apoptosis)

A mutation in the CARD domain of caspase-9 that prevents its binding to Apaf1.

(Apoptotic signals cause the release of cytochrome c from mitochondria and activation of apaf-1, which then cleaves the pro-enzyme of caspase-9 into the active dimer form. The CARD domain is needed to induce this cleavage)

Promoting Apoptosis:

A mutation in the BIR domain of the IAP protein DIAP1 that prevents binding to either caspases or anti-IAP proteins

(There is the loss of inhibition of apoptosis and therefore the caspases are free to function)