A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Specific cancer-associated mutations in the switch III region of Ras increase tumorigenicity by nanocluster augmentation




Julkaisun tekijät: Maja Šolman, Alessio Ligabue, Olga Blaževitš, Alok Jaiswal, Yong Zhou, Hong Liang, Benoit Lectez, Kari Kopra, Camilo Guzmán, Harri Härmä, John F Hancock, Tero Aittokallio, Daniel Abankwa
Julkaisuvuosi: 2015
Journal: eLife
Volyymi: 4
Sivujen määrä: 23
ISSN: 2050-084X
eISSN: 2050-084X

Tiivistelmä


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.


Ladattava julkaisu

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.




Last updated on 2019-21-08 at 20:04