Cells are tightly regulated by sophisticated systems. Among such systems, post-translational modification has been intensively studied, and the ubiquitin-proteasome system is one of the best-known proteolytic mechanisms for the timely destruction of regulatory proteins. As progress has been made in research on the ubiquitin-proteasome system, our understanding of fundamental regulatory circuits, such as the cell cycle and circadian rhythms, has progressed. Here, we focused on the SKP1-CUL1-F-box protein of E3 ubiquitin ligase, especially the F-box and additional characteristic domain-containing proteins, as adaptors for regulatory proteins. Accumulating evidence suggests that the F-box and additional characteristic domain-containing proteins are involved in a wide variety of cellular processes and pathogenesis. This raises the possibility that F-box and additional characteristic domain-containing proteins could be used as biomarkers for certain diseases.

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