Nikko Elina, Sullivan James A, Pelham Hugh R B
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
EMBO Rep. 2008 Dec;9(12):1216-21. doi: 10.1038/embor.2008.199. Epub 2008 Oct 24.
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.
酵母中的许多质膜蛋白会被泛素化并内吞，但它们如何被识别进行修饰仍不清楚。在这里，我们表明，当细胞暴露于镉离子时，锰转运蛋白Smf1会被内吞，这种内吞作用依赖于特定赖氨酸的Rsp5依赖性泛素化，并且还需要附近位点的磷酸化。然而，这种磷酸化是组成性的，而非应激诱导的。高效的泛素化需要Ecm21或Csr2，它们是一类酵母抑制蛋白样蛋白家族的两个成员，该家族包含几个PY基序并与Rsp5结合。Ecm21也与磷酸化的Smf1结合，在Rsp5与其底物之间建立了联系。含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，可能作为泛素连接酶衔接子发挥普遍作用。
