PMAIP1 and leukemia: Blocking the UPS can have several effects, which are summarized as follows: (1) reducing the levels of anti-apoptotic proteins (e.g., tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB)), (2) increasing the expression level of the pro-apoptotic protein Noxa, (3) activating the caspases-mediated apoptotic pathway, (4) degrading pro-survival proteins and inducing myeloid leukemia cell differentiation protein, and (5) inhibiting drug efflux transporters.