کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2130564 | 1086584 | 2013 | 14 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes](/preview/png/2130564.png)
The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub4) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub4 chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub4 was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub4 was constitutively internalized and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub4 was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis.
► A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively.
► Receptor fragmentation is not required for endocytosis of ErbB2.
► Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2.
► ErbB2-Ub4 is internalized clathrin-dependently.
Journal: Experimental Cell Research - Volume 319, Issue 3, 1 February 2013, Pages 32–45