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PMID:18319262
| Citation |
Trapasso, F, Pichiorri, F, Gaspari, M, Palumbo, T, Aqeilan, RI, Gaudio, E, Okumura, H, Iuliano, R, Di Leva, G, Fabbri, M, Birk, DE, Raso, C, Green-Church, K, Spagnoli, LG, Venuta, S, Huebner, K and Croce, CM (2008) Fhit interaction with ferredoxin reductase triggers generation of reactive oxygen species and apoptosis of cancer cells. J. Biol. Chem. 283:13736-44 |
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| Abstract |
Fhit protein is lost in most cancers, its restoration suppresses tumorigenicity, and virus-mediated FHIT gene therapy induces apoptosis and suppresses tumors in preclinical models. We have used protein cross-linking and proteomics methods to characterize a Fhit protein complex involved in triggering Fhit-mediated apoptosis. The complex includes Hsp60 and Hsp10 that mediate Fhit stability and may affect import into mitochondria, where it interacts with ferredoxin reductase, responsible for transferring electrons from NADPH to cytochrome P450 via ferredoxin. Viral-mediated Fhit restoration increases production of intracellular reactive oxygen species, followed by increased apoptosis of lung cancer cells under oxidative stress conditions; conversely, Fhit-negative cells escape apoptosis, carrying serious oxidative DNA damage that may contribute to an increased mutation rate. Characterization of Fhit interacting proteins has identified direct effectors of the Fhit-mediated apoptotic pathway that is lost in most cancers through loss of Fhit. |
| Links |
PubMed PMC2376222 Online version:10.1074/jbc.M709062200 |
| Keywords |
Acid Anhydride Hydrolases/metabolism; Apoptosis; Cell Line, Tumor; Chaperonin 10/chemistry; Chaperonin 60/chemistry; Cytosol/metabolism; DNA Damage; Ferredoxin-Nitrite Reductase/chemistry; Humans; Mitochondria/metabolism; Models, Biological; Mutation; Neoplasm Proteins/metabolism; Neoplasms/metabolism; Protein Binding; Reactive Oxygen Species |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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See also
References
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