Following Ariadne's thread: a new perspective on RBR ubiquitin ligases

Dawn M Wenzel,Rachel E Klevit

doi:10.1186/1741-7007-10-24

Dawn M Wenzel, Rachel E Klevit

Open Access

https://doi.org/10.1186/1741-7007-10-24

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Abstract

Ubiquitin signaling pathways rely on E3 ligases for effecting the final transfer of ubiquitin from E2 ubiquitin conjugating enzymes to a protein target. Here we re-evaluate the hybrid RING/HECT mechanism used by the E3 family RING-between-RINGs (RBRs) to transfer ubiquitin to substrates. We place RBRs into the context of current knowledge of HECT and RING E3s. Although not as abundant as the other types of E3s (there are only slightly more than a dozen RBR E3s in the human genome), RBRs are conserved in all eukaryotes and play important roles in biology. Re-evaluation of RBR ligases as RING/HECT E3s provokes new questions and challenges the field.

Highlights

Ubiquitin signaling pathways rely on E3 ligases for effecting the final transfer of ubiquitin from E2 ubiquitin conjugating enzymes to a protein target
We determined that Ariadne, the defining member of a subclass of RING-containing E3 ligases known as RING-between-RINGs (RBRs), blurs the line between RING and HECT-type E3s
In contrast to RING domains, which can occur at any position within a given protein, all known HECT domains are found at the carboxy-terminal end of their respective proteins

Summary

Introduction

Ubiquitin signaling pathways rely on E3 ligases for effecting the final transfer of ubiquitin from E2 ubiquitin conjugating enzymes to a protein target. Eukaryotic E3 ubiquitin ligases are generally identified by the presence of either a HECT or a RING domain. The ubiquitin-conjugated E2 binds to the RING1 domain of the RBR E3 ligase.

Results

Conclusion