Both SCFCdc4α and SCFCdc4γ are required for cyclin E turnover in cell lines that don’t overexpress cyclin E

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The ubiquitin-mediated turnover of cyclin E is regulated by phosphorylation and the activity of the ubiquitin ligase SCFCdc4 (also known as SCFFbw7). In 293A cells, SCF complexes containing two different Cdc4 isoforms, α and γ, are required for efficient cyclin E ubiquitylation. Whereas SCFCdc4γ ubiquitylates cyclin E directly, SCFCdc4α serves as a cofactor for Pin1-mediated prolyl isomerization of the cyclin E phosphodegron, essential to potentiate ubiquitylation. In the current study, we show that the requirement for both Cdc4α and γ is general, except in cell lines where cyclin E is expressed at an elevated level. Under these circumstances, Cdc4α is sufficient for cyclin E turnover. Furthermore, the requirement for Cdc4γ can be bypassed by ectopic overexpression of cyclin E.