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The pseudophosphatase STYX targets the F‐box of FBXW 7 and inhibits SCF FBXW7 function
Author(s) -
Reiterer Veronika,
FiguerasPuig Cristina,
Le Guerroue Francois,
Confalonieri Stefano,
Vecchi Manuela,
Jalapothu Dasaradha,
Kanse Sandip M,
Deshaies Raymond J,
Di Fiore Pier Paolo,
Behrends Christian,
Farhan Hesso
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694795
Subject(s) - interactome , biology , ubiquitin ligase , suppressor , protein subunit , f box protein , function (biology) , ubiquitin , microbiology and biotechnology , computational biology , cancer , biochemistry , genetics , gene
The F‐box protein FBXW 7 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 FBXW 7 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 FBXW 7. We show that STYX binds to the F‐box domain of FBXW 7 and disables its recruitment into the SCF complex. Therefore, STYX acts as a direct inhibitor of FBXW 7, affecting the cellular levels of its substrates. Furthermore, we find that levels of STYX and FBXW 7 are anti‐correlated in breast cancer patients, which affects disease prognosis. We propose the STYX – FBXW 7 interaction as a promising drug target for future investigations.