Specific cancer-associated mutations in the switch III region of Ras increase tumorigenicity by nanocluster augmentation

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http://hdl.handle.net/10138/161430

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Solman , M , Ligabue , A , Blazevits , O , Jaiswal , A , Zhou , Y , Liang , H , Lectez , B , Kopra , K , Guzman , C , Harma , H , Hancock , J F , Aittokallio , T & Abankwa , D 2015 , ' Specific cancer-associated mutations in the switch III region of Ras increase tumorigenicity by nanocluster augmentation ' eLife , vol. 4 , 08905 . DOI: 10.7554/eLife.08905

Title: Specific cancer-associated mutations in the switch III region of Ras increase tumorigenicity by nanocluster augmentation
Author: Solman, Maja; Ligabue, Alessio; Blazevits, Olga; Jaiswal, Alok; Zhou, Yong; Liang, Hong; Lectez, Benoit; Kopra, Kari; Guzman, Camilo; Harma, Harri; Hancock, John F.; Aittokallio, Tero; Abankwa, Daniel
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2015-08-14
Language: eng
Number of pages: 23
Belongs to series: eLife
ISSN: 2050-084X
URI: http://hdl.handle.net/10138/161430
Abstract: Hotspot mutations of Ras drive cell transformation and tumorigenesis. Less frequent mutations in Ras are poorly characterized for their oncogenic potential. Yet insight into their mechanism of action may point to novel opportunities to target Ras. Here, we show that several cancer-associated mutations in the switch III region moderately increase Ras activity in all isoforms. Mutants are biochemically inconspicuous, while their clustering into nanoscale signaling complexes on the plasma membrane, termed nanocluster, is augmented. Nanoclustering dictates downstream effector recruitment, MAPK-activity, and tumorigenic cell proliferation. Our results describe an unprecedented mechanism of signaling protein activation in cancer.
Subject: H-RAS
K-RAS
PLASMA-MEMBRANE
DEVELOPMENTAL DISORDERS
QUANTITATIVE-ANALYSIS
SIGNAL-TRANSDUCTION
PROTEIN-KINASE
FORMS DIMERS
NUCLEOTIDE
ORIENTATION
3111 Biomedicine
3122 Cancers
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