Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Pareja, F (Author) Other; Ferraro, DA (Author) Other; Rubin, C (Author) Other; Cohen Dvashi, H (Author) Other; Zhang, F (Author) Other; Aulmann, S (Author) Other; Ben Chetrit, N (Author) Other; Pines, G (Author) Other; Navon, R (Author) Other; Crosetto, N (Author) Other; Koestler, W (Author) Other; Carvalho, S (Author) Other; Lavi, S (Author) Other; Fernando Schmitt (Author) FMUP; Dikic, I (Author) Other; Yakhini, Z (Author) Other; Sinn, P (Author) Other; Mills, GB (Author) Other; Yarden, Y (Author) Other

Journal

Title: Oncogene

Vol. 31

Pages: 4599-4608

ISSN: 0950-9232

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 72 Citations

Scopus - 74 Citations

Other information

Authenticus ID: P-002-4TX

DOI: 10.1038/onc.2011.587

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10