UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling
2020
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.
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