Bul proteins, a nonredundant, antagonistic family of ubiquitin ligase regulatory proteins.
Bul proteins, a nonredundant, antagonistic family of ubiquitin ligase regulatory proteins.
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Bul 蛋白，一种非冗余、拮抗的泛素连接酶调节蛋白家族。
DOI：
10.1128/ec.00009-12
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Novoselova TV
中科院分区：
文献类型：
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作者：
Novoselova TV
与其他Nedd 4连接酶一样，酿酒酵母E3 Rsp 5 p利用接头蛋白与一些底物相互作用。以前的研究已经确定Bul 1 p和Bul 2 p作为接头蛋白，促进连接酶-底物相互作用。在这里，我们展示了Bul家族的第三个成员Bul 3 p的鉴定，Bul 3 p是两个相邻的开放阅读框架的产物，由一个经过通读翻译的终止密码子分隔。对BUL基因缺失的组合分析表明，它们调节已知涉及Rsp 5 p的一些但不是全部细胞通路。令人惊讶的是，我们发现Bul蛋白可以拮抗地调节相同的泛素依赖性过程，并且这种拮抗活性的性质在不同底物之间变化。我们进一步表明，使用vitroubiquitination测定，Bul蛋白对WW结构域具有不同的特异性，并且两种形式的Bul 3 p与Rsp 5 p的相互作用不同，可能导致交替的功能结果。这些数据引入了一个新的水平的复杂性，发生在Rsp 5 p和它的衔接子和底物之间的监管相互作用，并建议一个更关键的作用，Bul家族的蛋白质在控制衔接子介导的泛素化。
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 ofBULgene 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, usingin vitroubiquitination 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.