UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling
- Creators
- Torrino, Stéphanie
- Tiroille, Victor
- Dolfi, Bastien
- Dufies, Maeva
- Hinault, Charlotte
- Bonesso, Laurent
- Dagnino, Sonia
- Uhler, Jennifer
- Irondelle, Marie
- Gay, Anne-Sophie
- Fleuriot, Lucile
- Debayle, Delphine
- Lacas-Gervais, Sandra
- Cormont, Mireille
- Bertero, Thomas
- Bost, Frederic
- Gilleron, Jerome
- Clavel, Stephan
- Others:
- Centre méditerranéen de médecine moléculaire (C3M) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)
- Centre Scientifique de Monaco (CSM)
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Université Côte d'Azur (UCA)
- Centre National de la Recherche Scientifique (CNRS)
Description
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.
Abstract
International audience
Additional details
- URL
- https://hal.science/hal-03408303
- URN
- urn:oai:HAL:hal-03408303v1
- Origin repository
- UNICA