| Title: |
Specific cancer-associated mutations in the switch III region of Ras increase tumorigenicity by nanocluster augmentation |
| Authors: |
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 |
| Contributors: |
Institute for Molecular Medicine Finland; Tero Aittokallio / Principal Investigator; Bioinformatics |
| Publisher Information: |
ELIFE SCIENCES PUBLICATIONS LTD |
| Publication Year: |
2016 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
H-RAS; K-RAS; PLASMA-MEMBRANE; DEVELOPMENTAL DISORDERS; QUANTITATIVE-ANALYSIS; SIGNAL-TRANSDUCTION; PROTEIN-KINASE; FORMS DIMERS; NUCLEOTIDE; ORIENTATION; Biomedicine; Cancers |
| Description: |
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. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISBN: |
978-84-941364-4-3; 84-941364-4-5 |
| Relation: |
Suomen Akatemia (Academy of Finland) 272437, 269862, 279163 Tero Aittokallio; https://hdl.handle.net/10138/161430; 84941364451; 000373812900001 |
| Availability: |
https://hdl.handle.net/10138/161430 |
| Rights: |
info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.BA6C17D2 |
| Database: |
BASE |