Journal of Biomedical Science

, Volume 13, Issue 2, pp 181–191

F-box proteins: the key to protein degradation


DOI: 10.1007/s11373-005-9058-2

Cite this article as:
Ho, M.S., Tsai, PI. & Chien, CT. J Biomed Sci (2006) 13: 181. doi:10.1007/s11373-005-9058-2


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.


26S proteasome Ago Cullin E3 ligases F-box Morgue protein degradation SCF complex Slimb ubiquitination 
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Copyright information

© National Science Council Taipei 2006

Authors and Affiliations

  • Margaret S. Ho
    • 1
  • Pei-I Tsai
    • 2
  • Cheng-Ting Chien
    • 1
    • 2
  1. 1.Institute of Molecular BiologyAcademia SinicaTaipeiTaiwan
  2. 2.Institute of Molecular Medicine, Medical CollegeNational Taiwan UniversityTaipeiTaiwan

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