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Protein degradation

Tipping the balance

Nature Reviews Molecular Cell Biology volume 10, page 368 (2009)Cite this article

A new protein that regulates ubiquitin homeostasis has been identified by Keiji Tanaka and co-workers. As described in Cell, Rfu1 (regulator of free ubiquitin chains 1) regulates the concentrations of monomeric ubiquitin and free ubiquitin chains by inhibiting the deubiquitylating enzyme (DUB) Doa4.

Cells that lack Rfu1 accumulate monomeric ubiquitin and have reduced levels of free ubiquitin chains, whereas overexpression of Rfu1 has the opposite effect. These results suggest that Rfu1 inhibits the production of monomeric ubiquitin and promotes the formation of free ubiquitin chains. Of the 19 DUBs in yeast, only Doa4 localizes to endosomes in which Rfu1 is also present. Lack of Doa4 causes accumulation of free ubiquitin chains and reduction of the monomeric ubiquitin pool, which is the opposite effect of Rfu1 depletion. Furthermore, Rfu1 interacts with Doa4 in vitro and in vivo, and recombinant Rfu1 inhibits the deubiquitylating activity of Doa4 in vitro. So, Rfu1 is an inhibitor of Doa4.

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ORIGINAL RESEARCH PAPER

  1. Kimura, Y. et al. An inhibitor of a deubiquitinating enzyme regulates ubiquitin homeostasis. Cell 137, 549–559 (2009)

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Authors
  1. Francesca Cesari
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Cesari, F. Tipping the balance. Nat Rev Mol Cell Biol 10, 368 (2009). https://doi.org/10.1038/nrm2701

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