Fbw7/hCDC4 dimerization regulates its substrate interactions
作者： Markus Welcker , Bruce E Clurman
关键词: Substrate Interaction 、 Biology 、 Ubiquitin ligase 、 Binding site 、 Biophysics 、 Cyclin E 、 Phosphorylation 、 Amino acid 、 Function (biology) 、 Bioinformatics 、 Hyperphosphorylation
摘要: The Fbw7 ubiquitin ligase promotes the rapid degradation of several important oncogenes, such as cyclin E, c-Myc, c-Jun, and Notch. two fission yeast homologs Fbw7, pop1 pop2, have previously been shown to dimerize. In this study, we asked whether can also dimerize how dimerization affects function. We found that binds efficiently itself through a domain just upstream its F-box. further show is essential for stable interaction with E T380 phospho-degron. Surprisingly, requirement be suppressed by an additional phosphorylation phospho-degron at +4 position (S384), which creates binding site higher affinity monomeric Fbw7. Degradation pathway can, thus, conditionally regulated either or hyperphosphorylation Other substrates, cannot accommodate extra phosphate in their phospho-degrons, don't provide negatively charged amino acid position, may absolutely dependent on turnover. Our results point level regulation substrate turnover
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