Funational analysis of Rfu1 that regulates ubiquitin homeostasis

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Yeast Rfu1 (Regulator for free ubiquitin chain 1) localizes to endosomes and plays a role in ubiquitin homeostasis by inhibiting the activity of Doa4. We showed that Bro1 that recruits Doa4 to endosomes and stimulates Doa4 deubiquitinating activity, also recruits Rfu1 to endosomes. This recruitment is mediated by a direct interaction between the YPEL motif in the Rfu1 carboxyl-terminus and the V domain in Bro1. Furthermore, overexpression of Bro1, particularly the V domain, prevents Rfu1 degradation in response to heat shock. Thus, Bro1 regulates both the localization and stability of Rfu1. Rfu1 degradation involved the proteasome and a ubiquitin ligase Rsp5, suggesting that Rfu1 stability is regulated by ubiquitin-proteasome pathways.