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New Binding Target for Oncogenic Viral Protein

Simian virus 40 encodes the oncogenic large T antigen whose functions include the inactivation of tumor suppressor genes. The most well known targets of the T antigen are the retinoblastoma protein and p53. Markus Welcker and Bruce E. Clurman now report that the T antigen also binds to another tumor suppressor: the F-box substrate recognition subunit (Fbw7) of a Skp1/Cullin/F-box protein ubiquitin ligase complex. Interestingly, the F-box protein binds to the T antigen via a decoy phospho-epitope on the antigen's C terminus that mimics a consensus sequence found in the substrates of the F-box. However, unlike its bona fide substrates, the F-box protein does not degrade the T antigen. The authors propose that the T antigen may bind and titrate out the F-box protein, leading to enhanced levels of substrates normally degraded by the ubiquitin ligase complex, such as cyclin E.

The large T antigen contains a consensus sequence found in F-box substrates.

FOOTNOTES

See referenced article, J. Biol. Chem. 2005, 280, 7654-7658