共查询到20条相似文献,搜索用时 31 毫秒
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Magnifico A Ettenberg S Yang C Mariano J Tiwari S Fang S Lipkowitz S Weissman AM 《The Journal of biological chemistry》2003,278(44):43169-43177
Cbl proteins have RING finger-dependent ubiquitin ligase (E3) activity that is essential for down-regulation of tyrosine kinases. Here we establish that two WW domain HECT E3s, Nedd4 and Itch, bind Cbl proteins and target them for proteasomal degradation. This is dependent on the E3 activity of the HECT E3s but not on that of Cbl. Consistent with these observations, in cells expressing the epidermal growth factor receptor, Nedd4 reverses Cbl-b effects on receptor down-regulation, ubiquitylation, and proximal events in signaling. Cbl-b also targets active Src for degradation in cells, and Nedd4 similarly reverses Cbl-mediated Src degradation. These findings establish that RING finger E3s can be substrates, not only for autoubiquitylation but also for ubiquitylation by HECT E3s and suggest an additional level of regulation for Cbl substrates including protein-tyrosine kinases. 相似文献
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SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and medulloblastoma development 下载免费PDF全文
Madalina Raducu Ella Fung Sébastien Serres Paola Infante Alessandro Barberis Roman Fischer Claire Bristow Marie‐Laëtitia Thézénas Csaba Finta John C Christianson Francesca M Buffa Benedikt M Kessler Nicola R Sibson Lucia Di Marcotullio Rune Toftgård Vincenzo D'Angiolella 《The EMBO journal》2016,35(13):1400-1416
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Bhatia N Thiyagarajan S Elcheva I Saleem M Dlugosz A Mukhtar H Spiegelman VS 《The Journal of biological chemistry》2006,281(28):19320-19326
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《Cell cycle (Georgetown, Tex.)》2013,12(21):2457-2463
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The ubiquitously expressed mammalian Na+/H+ exchanger 1 (NHE1) controls cell volume and pH but is also critically involved in complex biological processes like cell adhesion, cell migration, cell proliferation, and mechanosensation. Pathways controlling NHE1 turnover at the plasma membrane, however, are currently unclear. Here, we demonstrate that NHE1 undergoes ubiquitylation at the plasma membrane by a process that is unprecedented for a mammalian ion transport protein. This process requires the adapter protein β-arrestin-1 that interacts with both the E3 ubiquitin ligase Nedd4-1 and the NHE1 C terminus. Truncation of NHE1 C terminus to amino acid 550 abolishes binding to β-arrestin-1 and NHE1 ubiquitylation. Overexpression of β-arrestin-1 or of wild type but not ligase-dead Nedd4-1 increases NHE1 ubiquitylation. siRNA-mediated knock-down of Nedd4-1 or β-arrestin-1 reduces NHE1 ubiquitylation and endocytosis leading to increased NHE1 surface levels. Fibroblasts derived from β-arrestin-1 and Nedd4-1 knock-out mice show loss of NHE1 ubiquitylation, increased plasmalemmal NHE1 levels and greatly enhanced NHE1 transport compared with wild-type fibroblasts. These findings reveal Nedd4-1 and β-arrestin-1 as key regulators of NHE1 ubiquitylation, endocytosis, and function. Our data suggest a broader role for β-arrestins in the regulation of membrane ion transport proteins than currently known. 相似文献
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Several PATCHED1 missense mutations display activity in patched1-deficient fibroblasts 总被引:3,自引:0,他引:3
Bailey EC Milenkovic L Scott MP Collawn JF Johnson RL 《The Journal of biological chemistry》2002,277(37):33632-33640
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