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.
Highlights
This article has been withdrawn by the authors because of errors that occurred in the construction of Figs. 1D, 3C, 5C, and 5H, and supplemental Fig. 1A have been brought to their attention
The authors state that the errors do not affect the conclusions of the article, which have been confirmed in subsequent articles
Summary
This article has been withdrawn by the authors because of errors that occurred in the construction of Figs. 1D, 3C, 5C, and 5H, and supplemental Fig. 1A have been brought to their attention.
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