Alternative splicing determines the domain structure of WWP1, a Nedd4 family protein
Alternative splicing determines the domain structure of WWP1, a Nedd4 family protein
复制标题
DOI：
10.1006/bbrc.2001.6206
复制
发表时间：
2002-01-11
影响因子：
3.1
通讯作者：
Baron, M
中科院分区：
文献类型：
--
作者：
Flasza, M;Gorman, P;Baron, M
Nedd-4 样蛋白是 E3 泛素连接酶分子，可调节关键的运输决策，包括将蛋白质靶向蛋白体或溶酶体。在这里，我们展示了人类 Nedd4 家族基因 WWP1 位于 8q21 上，并通过选择性剪接生成至少 6 个亚型。我们表明，选择性剪接会影响 WWP1 的结构域结构，其形式包含或缺乏 N 端 C2 结构域。有趣的是，这些形式的相对比例以组织特异性的方式变化。还鉴定出其他剪接形式，它们可能通过去除其预测的 C 末端 β 链来破坏 C2 结构域的结构。通过引入阅读框移位，一种剪接形式生成WWP1的仅C2结构域形式。我们讨论了这样的假设：剪接位点使用的调节可能会调节 WWP1 以及可能的其他 Nedd4 家族蛋白的活性。 (C) 2002 年爱思唯尔科学。
Nedd-4-like proteins are E3 ubiquitin-ligase molecules which regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Here we show that a human Nedd4 family gene, WWP1, is localized on 8q21 and generates at least six isoforms through alternative splicing. We show that alternative splicing affects the domain structure of WWP1, with forms that contain or lack an N-terminal C2 domain. Interestingly, the relative ratio of these forms varies in a tissue-specific manner. Other splice forms were also identified which may disrupt the structure of the C2 domain by removing its predicted C-terminal beta-strands. One splice form generates, through the introduction of a reading frame shift, a C2 domain-only form of WWP1. We discuss the hypothesis that regulation of splice site usage may modulate the activity of WWP1 and possibly other Nedd4 family proteins. (C) 2002 Elsevier Science.