UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling
| Title: | UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling |
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| Authors: | Stéphanie Torrino, Victor Tiroille, Bastien Dolfi, Maeva Dufies, Charlotte Hinault, Laurent Bonesso, Sonia Dagnino, Jennifer Uhler, Marie Irondelle, Anne-sophie Gay, Lucile Fleuriot, Delphine Debayle, Sandra Lacas-Gervais, Mireille Cormont, Thomas Bertero, Frederic Bost, Jerome Gilleron, Stephan Clavel |
| Source: | eLife, Vol 10 (2021) |
| Publisher Information: | eLife Sciences Publications Ltd, 2021. |
| Publication Year: | 2021 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | EGFR, UBTD1, ubiquitination, cell proliferation, ceramide, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | To adapt in an ever-changing environment, cells must integrate physical and chemical signals and translate them into biological meaningful information through complex signaling pathways. By combining lipidomic and proteomic approaches with functional analysis, we have shown that ubiquitin domain-containing protein 1 (UBTD1) plays a crucial role in both the epidermal growth factor receptor (EGFR) self-phosphorylation and its lysosomal degradation. On the one hand, by modulating the cellular level of ceramides through N-acylsphingosine amidohydrolase 1 (ASAH1) ubiquitination, UBTD1 controls the ligand-independent phosphorylation of EGFR. On the other hand, UBTD1, via the ubiquitination of Sequestosome 1 (SQSTM1/p62) by RNF26 and endolysosome positioning, participates in the lysosomal degradation of EGFR. The coordination of these two ubiquitin-dependent processes contributes to the control of the duration of the EGFR signal. Moreover, we showed that UBTD1 depletion exacerbates EGFR signaling and induces cell proliferation emphasizing a hitherto unknown function of UBTD1 in EGFR-driven human cell proliferation. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/68348; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.68348 |
| Access URL: | https://doaj.org/article/3b8ac826e8224f39920b2d2a0010217a |
| Accession Number: | edsdoj.3b8ac826e8224f39920b2d2a0010217a |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.68348 |
| Published in: | eLife |
| Language: | English |