Fbw7/hCDC4 dimerization regulates its substrate interactions

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

• Publication year

  2007

• Venue

  Cell Division

• Publication date

  2007-02-13

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/1747-1028-2-7PMID 17298674PMCID 1802738
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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