F-box proteins: the key to protein degradation.
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.
Ho
Margaret S
MS
Institute of Molecular Biology, Academia Sinica, 115, Taipei, Taiwan.
Tsai
Pei-I
PI
Chien
Cheng-Ting
CT
D000818:Animals; D029721:Drosophila Proteins; D044783:F-Box Proteins / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D029721:Drosophila Proteins; D044783:F-Box Proteins; D011506:Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases