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Title: OTUB1 triggers lung cancer development by inhibiting RAS monoubiquitination
Author: Baietti, Maria Francesca
Simicek, Michal
Abbasi Asbagh, Layka
Radaelli, Enrico
Lievens, Sam
Crowther, Jonathan
Steklov, Mikhail
Aushev, Vasily N.
Martínez García, David
Tavernier, Jan
Sablina, Anna A.
Keywords: Cisteïna
Càncer de pulmó
Proteïnes ras
Lung cancer
Ras proteins
Issue Date: 8-Feb-2016
Publisher: EMBO Press
Abstract: Activation of the RAS oncogenic pathway, frequently ensuing from mutations in RAS genes, is a common event in human cancer. Recent reports demonstrate that reversible ubiquitination of RAS GTPases dramatically affects their activity, suggesting that enzymes involved in regulating RAS ubiquitination may contribute to malignant transformation. Here, we identified the de-ubiquitinase OTUB1 as a negative regulator of RAS mono- and di-ubiquitination. OTUB1 inhibits RAS ubiquitination independently of its catalytic activity resulting in sequestration of RAS on the plasma membrane. OTUB1 promotes RAS activation and tumorigenesis in wild-type RAS cells. An increase of OTUB1 expression is commonly observed in non-small-cell lung carcinomas harboring wild-type KRAS and is associated with increased levels of ERK1/2 phosphorylation, high Ki67 score, and poorer patient survival. Our results strongly indicate that dysregulation of RAS ubiquitination represents an alternative mechanism of RAS activation during lung cancer development
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It is part of: EMBO Molecular Medicine, 2016, vol. 8, num. 3, p. 288-303
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ISSN: 1757-4676
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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