UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling.
Acid Ceramidase
/ genetics
Cell Line, Tumor
Cell Proliferation
Ceramides
/ metabolism
ErbB Receptors
/ genetics
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Kinetics
Lysosomes
/ enzymology
Male
Neoplasm Proteins
/ genetics
Phosphorylation
Prostatic Neoplasms
/ enzymology
Proteolysis
Sequestosome-1 Protein
/ genetics
Signal Transduction
Ubiquitination
Ubiquitins
/ genetics
EGFR
UBTD1
cell biology
cell proliferation
ceramide
human
ubiquitination
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
22 04 2021
22 04 2021
Historique:
received:
12
03
2021
accepted:
20
04
2021
pubmed:
23
4
2021
medline:
28
10
2021
entrez:
22
4
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33884955
doi: 10.7554/eLife.68348
pii: 68348
pmc: PMC8118655
doi:
pii:
Substances chimiques
Ceramides
0
Neoplasm Proteins
0
RNF26 protein, human
0
SQSTM1 protein, human
0
Sequestosome-1 Protein
0
UBTD1 protein, human
0
Ubiquitins
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
ASAH1 protein, human
EC 3.5.1.23
Acid Ceramidase
EC 3.5.1.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021, Torrino et al.
Déclaration de conflit d'intérêts
ST, VT, BD, MD, CH, LB, SD, JU, MI, AG, LF, DD, SL, MC, TB, FB, JG, SC No competing interests declared
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