Abstract:
:Endocytosis of signaling receptors, such as epidermal growth factor receptor (EGFR), tightly controls the signal transduction process triggered by ligand activation of these receptors. To identify new regulators of the endocytic trafficking of EGFR an RNA interference screen was performed for genes involved in ubiquitin conjugation and down-regulation of EGFR. The screen revealed that small interfering RNAs (siRNAs) that target the conserved ubiquitin-binding domain Uev1 increased down-regulation of EGFR. Since these siRNAs simultaneously targeted multiple genes containing a Uev1 domain, we analyzed the role of these gene products by overexpressing individual Uev1-related proteins. This analysis revealed that overexpression of Uev1A (UBE2V1) has no effect on the degradation of EGFR:EGF complexes. In contrast, overexpression of Uev1B (TMEM189-UBE2V1 isoform 2) slowed the degradation of EGF:receptor complexes. The Uev1B protein was found to strongly colocalize and associate with ubiquitin and Hrs in endosomes. Moreover, overexpression of Uev1B abrogated the ability of Hrs to colocalize with EGFR. The B-domain of Uev1B, and not the UEV-domain, was mainly responsible for the observed phenotypes suggesting the presence of a novel endosomal targeting sequence within the B-domain. Together, the data show that elevated levels of Uev1B protein in cells lead to decreased efficiency of endosomal sorting by associating with ubiquitinated proteins and Hrs.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Duex JE,Mullins MR,Sorkin Adoi
10.1016/j.yexcr.2010.04.017subject
Has Abstractpub_date
2010-08-01 00:00:00pages
2136-51issue
13eissn
0014-4827issn
1090-2422pii
S0014-4827(10)00185-0journal_volume
316pub_type
杂志文章abstract::Breast cancer (BC) is one of the most common cancers among women in both developed and developing countries with a rising incidence. Using the MMTV-PyMT transgenic mouse model and xenografted breast cancer model, we found that R5, a neutralizing antibody to Robo1, significantly inhibited BC growth and metastasis. Angi...
journal_title:Experimental cell research
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journal_title:Experimental cell research
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doi:10.1016/j.yexcr.2016.12.025
更新日期:2017-02-01 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1006/excr.1995.1362
更新日期:1995-11-01 00:00:00
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doi:10.1016/0014-4827(89)90331-5
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(84)90593-7
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pub_type: 杂志文章
doi:10.1006/excr.1993.1297
更新日期:1993-11-01 00:00:00
abstract::Cells with and without hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity were used to examine the transfer of purine metabolites through the medium and via cell contacts. HGPRT- Chinese hamster and human fibroblasts were able to incorporate 3H-labeled purine metabolite(s) from medium in which mouse HGPRT...
journal_title:Experimental cell research
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1016/j.yexcr.2004.08.043
更新日期:2004-12-10 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(86)90204-1
更新日期:1986-11-01 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
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更新日期:1993-10-01 00:00:00
abstract::High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression usin...
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doi:10.1016/j.yexcr.2012.01.014
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