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.
Ploner
C
C
Division of Molecular Pathophysiology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
Kofler
R
R
Villunger
A
A
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002648:Child; D004249:DNA Damage; D005786:Gene Expression Regulation; D006801:Humans; D007448:Invertebrates / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014714:Vertebrates / Q000378:metabolism
C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; C498702:PMAIP1 protein, human; C408009:Pmaip1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D013755:Tetradecanoylphorbol Acetate