Bibliographic Details
| Title: |
KRAS Engages AGO2 to Enhance Cellular Transformation |
| Authors: |
Sunita Shankar, Sethuramasundaram Pitchiaya, Rohit Malik, Vishal Kothari, Yasuyuki Hosono, Anastasia K. Yocum, Harika Gundlapalli, Yasmine White, Ari Firestone, Xuhong Cao, Saravana M. Dhanasekaran, Jeanne A. Stuckey, Gideon Bollag, Kevin Shannon, Nils G. Walter, Chandan Kumar-Sinha, Arul M. Chinnaiyan |
| Source: |
Cell Reports, Vol 14, Iss 6, Pp 1448-1461 (2016) |
| Publisher Information: |
Elsevier, 2016. |
| Publication Year: |
2016 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
cancer, KRAS, EIF2C2, Argonaute 2, RNA silencing, Biology (General), QH301-705.5 |
| More Details: |
Oncogenic mutations in RAS provide a compelling yet intractable therapeutic target. Using co-immunoprecipitation mass spectrometry, we uncovered an interaction between RAS and Argonaute 2 (AGO2). Endogenously, RAS and AGO2 co-sediment and co-localize in the endoplasmic reticulum. The AGO2 N-terminal domain directly binds the Switch II region of KRAS, agnostic of nucleotide (GDP/GTP) binding. Functionally, AGO2 knockdown attenuates cell proliferation in mutant KRAS-dependent cells and AGO2 overexpression enhances KRASG12V-mediated transformation. Using AGO2−/− cells, we demonstrate that the RAS-AGO2 interaction is required for maximal mutant KRAS expression and cellular transformation. Mechanistically, oncogenic KRAS attenuates AGO2-mediated gene silencing. Overall, the functional interaction with AGO2 extends KRAS function beyond its canonical role in signaling. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124716000553; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2016.01.034 |
| Access URL: |
https://doaj.org/article/f133faf0e1bf409685a3407f3bf3ecbb |
| Accession Number: |
edsdoj.f133faf0e1bf409685a3407f3bf3ecbb |
| Database: |
Directory of Open Access Journals |
