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The pseudophosphatase STYX targets the F‐box of FBXW7 and inhibits SCF<sup>FBXW7</sup> function

The pseudophosphatase STYX targets the F‐box of FBXW7 and inhibits SCFFBXW7 function

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REITERER, Veronika, Francois LE GUERROUE, Stefano CONFALONIERI, Manuela VECCHI, Dasaradha JALAPOTHU, Sandip M KANSE, Raymond J. DESHAIES, Pier Paolo DI FIORE, Christian BEHRENDS, Hesso FARHAN, 2017. The pseudophosphatase STYX targets the F‐box of FBXW7 and inhibits SCFFBXW7 function. In: The EMBO Journal. 36(3), pp. 260-273. ISSN 0261-4189. eISSN 1460-2075. Available under: doi: 10.15252/embj.201694795

@article{Reiterer2017pseud-38846, title={The pseudophosphatase STYX targets the F‐box of FBXW7 and inhibits SCFFBXW7 function}, year={2017}, doi={10.15252/embj.201694795}, number={3}, volume={36}, issn={0261-4189}, journal={The EMBO Journal}, pages={260--273}, author={Reiterer, Veronika and Le Guerroue, Francois and Confalonieri, Stefano and Vecchi, Manuela and Jalapothu, Dasaradha and Kanse, Sandip M and Deshaies, Raymond J. and Di Fiore, Pier Paolo and Behrends, Christian and Farhan, Hesso} }

Di Fiore, Pier Paolo Di Fiore, Pier Paolo Kanse, Sandip M The F-box protein FBXW7 is the substrate-recruiting subunit of an SCF ubiquitin ligase and a major tumor-suppressor protein that is altered in several human malignancies. Loss of function of FBXW7 results in the stabilization of numerous proteins that orchestrate cell proliferation and survival. Little is known about proteins that directly regulate the function of this protein. In the current work, we have mapped the interactome of the enigmatic pseudophosphatase STYX We reasoned that a catalytically inactive phosphatase might have adopted novel mechanisms of action. The STYX interactome contained several F-box proteins, including FBXW7. We show that STYX binds to the F-box domain of FBXW7 and disables its recruitment into the SCF complex. Therefore, STYX acts as a direct inhibitor of FBXW7, affecting the cellular levels of its substrates. Furthermore, we find that levels of STYX and FBXW7 are anti-correlated in breast cancer patients, which affects disease prognosis. We propose the STYX-FBXW7 interaction as a promising drug target for future investigations. Confalonieri, Stefano Farhan, Hesso Vecchi, Manuela The pseudophosphatase STYX targets the F‐box of FBXW7 and inhibits SCF<sup>FBXW7</sup> function Reiterer, Veronika Le Guerroue, Francois Behrends, Christian eng Farhan, Hesso Jalapothu, Dasaradha Jalapothu, Dasaradha Kanse, Sandip M Confalonieri, Stefano Deshaies, Raymond J. Deshaies, Raymond J. 2017-05-11T10:08:52Z Le Guerroue, Francois Vecchi, Manuela 2017 Reiterer, Veronika 2017-05-11T10:08:52Z Behrends, Christian

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