UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling

Autor: S Torrino, V Tiroille, B Dolfi, M Dufies, C Hinault, L Bonesso, S Dagnino, JP Uhler, M Irondelle, AS Gay, L Fleuriot, D Debayle, S Lacas-Gervais, M Cormont, T Bertero, F Bost, J Gilleron, S Clavel
Přispěvatelé: Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 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), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Centre National de la Recherche Scientifique (CNRS), ANR-18-CE14-0025,MatriPHate,Comprendre la dynamique de la niche vasculaire dans l'hypertension pulmonaire.(2018), Centre Hospitalier Universitaire de Nice (CHU Nice), Imperial College London, University of Gothenburg (GU), 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), Bertero, Thomas, Bost, Frédéric
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Acid Ceramidase
[SDV]Life Sciences [q-bio]
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
chemistry.chemical_compound
0302 clinical medicine
Ubiquitin
Sequestosome-1 Protein
cell biology
Epidermal growth factor receptor
Biology (General)
Phosphorylation
0303 health sciences
education.field_of_study
biology
Neoplasm Proteins
Cell biology
ErbB Receptors
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
Medicine
Signal transduction
Signal Transduction
Ceramide
QH301-705.5
Science
EGFR
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Ceramides
ubiquitination
Gene Expression Regulation
Enzymologic
UBTD1
03 medical and health sciences
Sequestosome 1
[SDV.CAN] Life Sciences [q-bio]/Cancer
Cell Line
Tumor
[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Humans
ceramide
human
education
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
Ubiquitins
030304 developmental biology
Cell growth
Prostatic Neoplasms
Endolysosome
Kinetics
cell proliferation
chemistry
Proteolysis
biology.protein
Lysosomes
Zdroj: eLife
eLife, eLife Sciences Publication, 2021, 10, ⟨10.7554/elife.68348⟩
eLife, eLife Sciences Publication, 2021, 10, ⟨10.7554/eLife.68348⟩
eLife, 2021, 10, ⟨10.7554/elife.68348⟩
eLife, Vol 10 (2021)
eLife, 2021, 10, ⟨10.7554/eLife.68348⟩
ISSN: 2050-084X
Popis: 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 UBTD1 (Ubiquitin domain-containing protein 1) plays a crucial role in both the EGFR (Epidermal Growth Factor Receptor) self-phosphorylation and its lysosomal degradation. On the one hand, by modulating the cellular level of ceramides through ASAH1 (N-Acylsphingosine Amidohydrolase 1) ubiquitination, UBTD1 controls the ligand-independent phosphorylation of EGFR. On the other hand, UBTD1, via the ubiquitination of SQSTM1/p62 (Sequestosome 1) 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 EGF-driven cell proliferation.
Databáze: OpenAIRE
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