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SCFs in the new millennium

Oncogene volume 33, pages 2011–2018 (2014)Cite this article

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Abstract

Substrate-specific degradation is a key feature of the ubiquitin proteasome system. Substrate specificity is typically directed by the E3 or ubiquitin ligase; such specificity can be conferred either by ligase modification or expression or conversely via modification of substrates that permit their recognition by a specific E3 ligase. The most well-known example of such complexes are the Cullin-RING ligases (CRLs). CRLs are composed of one of seven cullin-family scaffold proteins; the CRL serves as a scaffold that interacts directly with a RING-domain enzyme (Rbx1/2) through an extensive protein–protein interface within the globular C-terminal domain. At the N terminus, the cullin associates with an adaptor protein through cullin-repeat motifs. This adaptor, in turn, facilitates recruitment of a substrate-specifying factor that recruits the target to be ubiquitylated. The prototypical CRL is the cul1-containing complex, commonly referred to as the Skp1-Cul1-Fbox (SCF) ligase. SCF ligases contribute to the timely destruction of numerous substrates thereby ensuring normal cell growth. The importance of SCF function is highlighted by cancer-specific alterations in either the expression or the function of select F-box substrate-specific adaptors that results in neoplastic conversion. Herein, we discuss the current understanding of SCF function and contribution to cell biology.

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Acknowledgements

This work was supported by CA133154.

Author information

Authors and Affiliations

  1. Leonard and Madlyn Abramson Family Cancer Research Institute, Philadelphia, PA, USA

    E K Lee & J A Diehl

  2. Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    E K Lee & J A Diehl

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  1. E K Lee
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  2. J A Diehl
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Correspondence to J A Diehl.

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Lee, E., Diehl, J. SCFs in the new millennium. Oncogene 33, 2011–2018 (2014). https://doi.org/10.1038/onc.2013.144

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  • DOI: https://doi.org/10.1038/onc.2013.144

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