Arrestin-like proteins mediate ubiquitination and endocytosis of the yeast metal transporter Smf1
Arrestin-like proteins mediate ubiquitination and endocytosis of the yeast metal transporter Smf1
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DOI：
10.1038/embor.2008.199
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发表时间：
2008-12-01
期刊：
影响因子：
7.7
通讯作者：
Pelham, Hugh R. B.
中科院分区：
文献类型：
--
作者：
Nikko, Elina;Sullivan, James A.;Pelham, Hugh R. B.
酵母中的许多质膜蛋白被泛素化并被内吞，但它们如何被识别以进行修饰仍然是未知的。在这里，我们表明，锰转运蛋白Smf1是内吞细胞暴露于镉离子时，这种内吞依赖于Rsp5依赖的泛素化的特定赖氨酸，它也需要在附近的网站磷酸化。然而，这种磷酸化是组成性的，而不是应激诱导的。有效的泛素化需要Ecm 21或Csr2，这两个成员是一个含有几个PY基序并与Rsp 5结合的抑制蛋白样酵母蛋白家族。Ecm21还与磷酸化Smf1结合，提供Rsp5与其底物之间的连接。含有PY基序的抑制蛋白样蛋白存在于包括人类在内的许多物种中，并且可能具有作为泛素连接酶衔接子的一般作用。
Many plasma membrane proteins in yeast are ubiquitinated and endocytosed, but how they are recognized for modification has remained unknown. Here, we show that the manganese transporter Smf1 is endocytosed when cells are exposed to cadmium ions, that this endocytosis depends on Rsp5-dependent ubiquitination of specific lysines and that it also requires phosphorylation at nearby sites. This phosphorylation is, however, constitutive rather than stress-induced. Efficient ubiquitination requires Ecm21 or Csr2, two members of a family of arrestin-like yeast proteins that contain several PY motifs and bind to Rsp5. Ecm21 also binds to phosphorylated Smf1, providing a link between Rsp5 and its substrate. PY motif-containing arrestin-like proteins are found in many species, including humans, and might have a general role as ubiquitin ligase adaptors.