Bul proteins, a nonredundant, antagonistic family of ubiquitin ligase regulatory proteins

Novoselova, Tatiana ORCID logoORCID: https://orcid.org/0000-0002-2394-4667, Zahira, Kiran, Rose, Ruth-Sarah and Sullivan, James A. (2012) Bul proteins, a nonredundant, antagonistic family of ubiquitin ligase regulatory proteins. Eukaryotic Cell, 11 (4) . pp. 463-470. ISSN 1535-9778 [Article] (doi:10.1128/EC.00009-12)


Like other Nedd4 ligases, Saccharomyces cerevisiae E3 Rsp5p utilizes adaptor proteins to interact with some substrates. Previous studies have indentified Bul1p and Bul2p as adaptor proteins that facilitate the ligase-substrate interaction. Here, we show the identification of a third member of the Bul family, Bul3p, the product of two adjacent open reading frames separated by a stop codon that undergoes readthrough translation. Combinatorial analysis of BUL gene deletions reveals that they regulate some, but not all, of the cellular pathways known to involve Rsp5p. Surprisingly, we find that Bul proteins can act antagonistically to regulate the same ubiquitin-dependent process, and the nature of this antagonistic activity varies between different substrates. We further show, using in vitro ubiquitination assays, that the Bul proteins have different specificities for WW domains and that the two forms of Bul3p interact differently with Rsp5p, potentially leading to alternate functional outcomes. These data introduce a new level of complexity into the regulatory interactions that take place between Rsp5p and its adaptors and substrates and suggest a more critical role for the Bul family of proteins in controlling adaptor-mediated ubiquitination

Item Type: Article
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 28135
Useful Links:
Depositing User: Tatiana Novoselova
Date Deposited: 11 Nov 2019 17:04
Last Modified: 11 Nov 2019 17:04
URI: https://eprints.mdx.ac.uk/id/eprint/28135

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