Phosphoproteomic analysis identifies the tumor suppressor PDCD4 as a RSK substrate negatively regulated by 14-3-3
Abstract
The RSK family is a group of Ser/Thr kinases that promotes cell growth and proliferation in response to the Ras/MAPK pathway. Deregulated RSK activity has been associated with different disorders and diseases, such as cancer, but relatively little is known regarding the contribution of RSK to tumorigenesis. In this study, we describe, to our knowledge, the first global quantitative phosphoproteomic screen to characterize RSK-dependent signaling events in melanoma. Our results show that RSK negatively regulates the tumor suppressor PDCD4 by promoting its association to 14-3-3 proteins and subsequent proteasomal degradation. These findings further implicate RSK as a promising therapeutic target for the treatment of melanoma and suggest that RSK plays widespread biological functions downstream of the Ras/MAPK pathway.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- July 2014
- DOI:
- 10.1073/pnas.1405601111
- Bibcode:
- 2014PNAS..111E2918G