Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression

F. Pareja, D. A. Ferraro, C. Rubin, H. Cohen-Dvashi, F. Zhang, S. Aulmann, N. Ben-Chetrit, G. Pines, R. Navon, N. Crosetto, W. Köstler, S. Carvalho, S. Lavi, F. Schmitt, I. Dikic, Z. Yakhini, P. Sinn, Gordon Mills, Y. Yarden

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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 transphosphorylation 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.

Original languageEnglish (US)
Pages (from-to)4599-4608
Number of pages10
JournalOncogene
Volume31
Issue number43
DOIs
StatePublished - Oct 25 2012
Externally publishedYes

Fingerprint

Epidermal Growth Factor Receptor
Ubiquitin
Breast Neoplasms
Neoplasms
Growth Factor Receptors
Ligases
Growth
RNA Interference
Epidermal Growth Factor
Phosphorylation
Enzymes
Genes

Keywords

  • deubiquitination
  • endocytosis
  • gene amplification
  • growth factor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Pareja, F., Ferraro, D. A., Rubin, C., Cohen-Dvashi, H., Zhang, F., Aulmann, S., ... Yarden, Y. (2012). Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression. Oncogene, 31(43), 4599-4608. https://doi.org/10.1038/onc.2011.587

Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression. / Pareja, F.; Ferraro, D. A.; Rubin, C.; Cohen-Dvashi, H.; Zhang, F.; Aulmann, S.; Ben-Chetrit, N.; Pines, G.; Navon, R.; Crosetto, N.; Köstler, W.; Carvalho, S.; Lavi, S.; Schmitt, F.; Dikic, I.; Yakhini, Z.; Sinn, P.; Mills, Gordon; Yarden, Y.

In: Oncogene, Vol. 31, No. 43, 25.10.2012, p. 4599-4608.

Research output: Contribution to journalArticle

Pareja, F, Ferraro, DA, Rubin, C, Cohen-Dvashi, H, Zhang, F, Aulmann, S, Ben-Chetrit, N, Pines, G, Navon, R, Crosetto, N, Köstler, W, Carvalho, S, Lavi, S, Schmitt, F, Dikic, I, Yakhini, Z, Sinn, P, Mills, G & Yarden, Y 2012, 'Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression', Oncogene, vol. 31, no. 43, pp. 4599-4608. https://doi.org/10.1038/onc.2011.587
Pareja F, Ferraro DA, Rubin C, Cohen-Dvashi H, Zhang F, Aulmann S et al. Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression. Oncogene. 2012 Oct 25;31(43):4599-4608. https://doi.org/10.1038/onc.2011.587
Pareja, F. ; Ferraro, D. A. ; Rubin, C. ; Cohen-Dvashi, H. ; Zhang, F. ; Aulmann, S. ; Ben-Chetrit, N. ; Pines, G. ; Navon, R. ; Crosetto, N. ; Köstler, W. ; Carvalho, S. ; Lavi, S. ; Schmitt, F. ; Dikic, I. ; Yakhini, Z. ; Sinn, P. ; Mills, Gordon ; Yarden, Y. / Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression. In: Oncogene. 2012 ; Vol. 31, No. 43. pp. 4599-4608.
@article{1db59922c15c491caadd9fd9dd958811,
title = "Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression",
abstract = "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 transphosphorylation 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.",
keywords = "deubiquitination, endocytosis, gene amplification, growth factor",
author = "F. Pareja and Ferraro, {D. A.} and C. Rubin and H. Cohen-Dvashi and F. Zhang and S. Aulmann and N. Ben-Chetrit and G. Pines and R. Navon and N. Crosetto and W. K{\"o}stler and S. Carvalho and S. Lavi and F. Schmitt and I. Dikic and Z. Yakhini and P. Sinn and Gordon Mills and Y. Yarden",
year = "2012",
month = "10",
day = "25",
doi = "10.1038/onc.2011.587",
language = "English (US)",
volume = "31",
pages = "4599--4608",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "43",

}

TY - JOUR

T1 - Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression

AU - Pareja, F.

AU - Ferraro, D. A.

AU - Rubin, C.

AU - Cohen-Dvashi, H.

AU - Zhang, F.

AU - Aulmann, S.

AU - Ben-Chetrit, N.

AU - Pines, G.

AU - Navon, R.

AU - Crosetto, N.

AU - Köstler, W.

AU - Carvalho, S.

AU - Lavi, S.

AU - Schmitt, F.

AU - Dikic, I.

AU - Yakhini, Z.

AU - Sinn, P.

AU - Mills, Gordon

AU - Yarden, Y.

PY - 2012/10/25

Y1 - 2012/10/25

N2 - 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 transphosphorylation 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.

AB - 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 transphosphorylation 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.

KW - deubiquitination

KW - endocytosis

KW - gene amplification

KW - growth factor

UR - http://www.scopus.com/inward/record.url?scp=84867900349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867900349&partnerID=8YFLogxK

U2 - 10.1038/onc.2011.587

DO - 10.1038/onc.2011.587

M3 - Article

VL - 31

SP - 4599

EP - 4608

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 43

ER -