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Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression

Once stimulated, the epidermal growth factor receptor (EGFR) undergoes self-phosphorylation, which, on the one hand, instigates signaling cascades, and on the other hand, recruits CBL ubiquitin ligases, which mark EGFRs for degradation. Using RNA interference screens, we identified a deubiquitinatin...

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Autores principales: Pareja, Fresia, Ferraro, Daniela Aleida, Rubin, Chanan, Cohen-Dvashi, Hadas, Zhang, Fan, Aulmann, Sebastian, Ben-Chetrit, Nir, Pines, Gur, Navon, Roy, Crosetto, Nicola, Köstler, Wolfgang, Carvalho, Silvia, Lavi, Sara, Schmitt, Fernando, Dikic, Ivan, Yakhini, Zohar, Sinn, Peter, Mills, Gordon B., Yarden, Yosef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326441/
https://www.ncbi.nlm.nih.gov/pubmed/22179831
http://dx.doi.org/10.1038/onc.2011.587
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author Pareja, Fresia
Ferraro, Daniela Aleida
Rubin, Chanan
Cohen-Dvashi, Hadas
Zhang, Fan
Aulmann, Sebastian
Ben-Chetrit, Nir
Pines, Gur
Navon, Roy
Crosetto, Nicola
Köstler, Wolfgang
Carvalho, Silvia
Lavi, Sara
Schmitt, Fernando
Dikic, Ivan
Yakhini, Zohar
Sinn, Peter
Mills, Gordon B.
Yarden, Yosef
author_facet Pareja, Fresia
Ferraro, Daniela Aleida
Rubin, Chanan
Cohen-Dvashi, Hadas
Zhang, Fan
Aulmann, Sebastian
Ben-Chetrit, Nir
Pines, Gur
Navon, Roy
Crosetto, Nicola
Köstler, Wolfgang
Carvalho, Silvia
Lavi, Sara
Schmitt, Fernando
Dikic, Ivan
Yakhini, Zohar
Sinn, Peter
Mills, Gordon B.
Yarden, Yosef
author_sort Pareja, Fresia
collection PubMed
description Once stimulated, the epidermal growth factor receptor (EGFR) undergoes self-phosphorylation, which, on the one hand, instigates signaling cascades, and on the other hand, recruits CBL ubiquitin ligases, which mark EGFRs for degradation. Using RNA interference screens, we identified a deubiquitinating enzyme, Cezanne-1, that opposes receptor degradation and enhances EGFR signaling. These functions require the catalytic and ubiquitin-binding domains of Cezanne-1, and they involve physical interactions and trans-phosphorylaton of Cezanne-1 by EGFR. In line with the ability of Cezanne-1 to augment EGF-induced growth and migration signals, the enzyme is overexpressed in breast cancer. Congruently, the corresponding gene is amplified in approximately one third of mammary tumors, and high transcript levels predict an aggressive disease course. In conclusion, deubiquitination by Cezanne-1 curtails degradation of growth factor receptors, thereby promotes oncogenic growth signals.
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spelling pubmed-33264412013-04-25 Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression Pareja, Fresia Ferraro, Daniela Aleida Rubin, Chanan Cohen-Dvashi, Hadas Zhang, Fan Aulmann, Sebastian Ben-Chetrit, Nir Pines, Gur Navon, Roy Crosetto, Nicola Köstler, Wolfgang Carvalho, Silvia Lavi, Sara Schmitt, Fernando Dikic, Ivan Yakhini, Zohar Sinn, Peter Mills, Gordon B. Yarden, Yosef Oncogene Article Once stimulated, the epidermal growth factor receptor (EGFR) undergoes self-phosphorylation, which, on the one hand, instigates signaling cascades, and on the other hand, recruits CBL ubiquitin ligases, which mark EGFRs for degradation. Using RNA interference screens, we identified a deubiquitinating enzyme, Cezanne-1, that opposes receptor degradation and enhances EGFR signaling. These functions require the catalytic and ubiquitin-binding domains of Cezanne-1, and they involve physical interactions and trans-phosphorylaton of Cezanne-1 by EGFR. In line with the ability of Cezanne-1 to augment EGF-induced growth and migration signals, the enzyme is overexpressed in breast cancer. Congruently, the corresponding gene is amplified in approximately one third of mammary tumors, and high transcript levels predict an aggressive disease course. In conclusion, deubiquitination by Cezanne-1 curtails degradation of growth factor receptors, thereby promotes oncogenic growth signals. 2011-12-19 2012-10-25 /pmc/articles/PMC3326441/ /pubmed/22179831 http://dx.doi.org/10.1038/onc.2011.587 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Pareja, Fresia
Ferraro, Daniela Aleida
Rubin, Chanan
Cohen-Dvashi, Hadas
Zhang, Fan
Aulmann, Sebastian
Ben-Chetrit, Nir
Pines, Gur
Navon, Roy
Crosetto, Nicola
Köstler, Wolfgang
Carvalho, Silvia
Lavi, Sara
Schmitt, Fernando
Dikic, Ivan
Yakhini, Zohar
Sinn, Peter
Mills, Gordon B.
Yarden, Yosef
Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression
title Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression
title_full Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression
title_fullStr Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression
title_full_unstemmed Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression
title_short Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression
title_sort deubiquitination of egfr by cezanne-1 contributes to cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326441/
https://www.ncbi.nlm.nih.gov/pubmed/22179831
http://dx.doi.org/10.1038/onc.2011.587
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