Proteomics

Dataset Information

63

EGF-dependent ubiquitinome, phosphorylation and interactome analysis in control and CYLD-deficient cells


ABSTRACT: Cylindromatosis tumor suppressor protein (CYLD) is deubiquitinase, best known as an essential negative regulator of the NFkB pathway. Previous studies have suggested an involvement of CYLD in epidermal growth factor (EGF)-dependent signal transduction as well, as it was found enriched within the tyrosine-phosphorylated complexes in cells stimulated with the growth factor. EGF receptor (EGFR) signaling participates in central cellular processes and its tight regulation, partly through ubiquitination cascades, is decisive for a balanced cellular homeostasis. Here, using a combination of mass spectrometry-based quantitative proteomic approaches with biochemical and immunofluorescence strategies, we demonstrate the involvement of CYLD in the regulation of the ubiquitination events triggered by EGF. Our data show that CYLD regulates the magnitude of ubiquitination of several major effectors of the EGFR pathway by assisting the recruitment of the ubiquitin ligase Cbl-b to the activated EGFR complex. Notably, the deficiency of CYLD impairs the interaction of EGFR with Cbl-b, which leads to a reduced ubiquitination of the receptor followed by its decreased degradation. This represents a previously uncharacterized strategy exerted by this deubiquitinase and tumors pressor for the negative regulation of a tumorigenic signaling pathway.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo sapiens  

TISSUE(S): Hela Cell

DISEASE(S): Not Available

SUBMITTER: Michele Puglia  

LAB HEAD: Blagoy Blagoev

PROVIDER: PXD006390 | Pride | 2017-06-05

REPOSITORIES: Pride

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Publications

Cylindromatosis Tumor Suppressor Protein (CYLD) Deubiquitinase is Necessary for Proper Ubiquitination and Degradation of the Epidermal Growth Factor Receptor.

Sanchez-Quiles Virginia V   Akimov Vyacheslav V   Osinalde Nerea N   Francavilla Chiara C   Puglia Michele M   Barrio-Hernandez Inigo I   Kratchmarova Irina I   Olsen Jesper V JV   Blagoev Blagoy B  

Molecular & cellular proteomics : MCP 20170601 8


Cylindromatosis tumor suppressor protein (CYLD) is a deubiquitinase, best known as an essential negative regulator of the NFkB pathway. Previous studies have suggested an involvement of CYLD in epidermal growth factor (EGF)-dependent signal transduction as well, as it was found enriched within the tyrosine-phosphorylated complexes in cells stimulated with the growth factor. EGF receptor (EGFR) signaling participates in central cellular processes and its tight regulation, partly through ubiquitin  ...[more]

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