Summary
The eukaryotic protein degradation pathway involves the ubiquitin (Ub) modification of substrates targeted for degradation by the 26S proteasome. The addition of Ub, a process called ubiquitination, is mediated by enzymes including the E3 Ub ligases which transfer the Ub to targeted substrates. A major type of E3 Ub ligases, the SCF (Skp–Cullin–F-box) complex, is composed of four major components: Skp1, Cul1/Cdc53, Roc1/Rbx1/Hrt1, and an F-box protein. The F-box component of the SCF machineries is responsible for recognizing different substrates for ubiquitination. Interaction with components of the SCF complex is mediated through the F-box motif of the F-box protein while it associates with phosphorylated substrates through its second protein–protein interaction motif such as Trp–Asp (WD) repeats or leucine-rich repeats (LRRs). By targeting diverse substrates, F-box proteins exert controls over stability of proteins and regulate the mechanisms for a wide-range of cellular processes. Here we discuss the importance of F-box proteins by providing a general overview and examples of how F-box proteins function in various cellular settings such as tissue development, cell proliferation, and cell death, in the modeling organism Drosophila.
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Acknowledgements
We are grateful to C-Y. Ou and J-T. Wu for comments on this manuscript. C-T. Chien is supported by grants from the National Science Council and Academia Sinica of Taiwan. M. Ho is supported by postdoctoral fellowships from Academia Sinica of Taiwan.
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Ho, M.S., Tsai, PI. & Chien, CT. F-box proteins: the key to protein degradation. J Biomed Sci 13, 181–191 (2006). https://doi.org/10.1007/s11373-005-9058-2
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DOI: https://doi.org/10.1007/s11373-005-9058-2