Noxa: at the tip of the balance between life and death

Among all Bcl2 homology domain 3 (BH3)-only proteins known to date, APR/PMAIP1/Noxa, albeit showing weak proapoptotic potential on its own, appears to be crucial in fine-tuning cell death decisions by targeting the prosurvival molecule Mcl1 for proteasomal degradation. This event appears critical for cell death induction along the mitochondrial Bcl2-regulated apoptosis pathway in response to factor deprivation or DNA damage, presumably by sensitizing the cell toward the action of additional BH3-only protein family members. This review aims to summarize the function of Noxa in normal physiology, stress-induced cell death and tumorigenesis.