Neuroscience Information Framework

Options
Only Pubmed Central
Include Pubmed Central
Sections
Title
Abstract
Introduction
Methods
Results
Supplement
Appendix
Contributions
Background
Commentary
Funding
Limitations
Caption
FILTERS

ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation.

Authors:
Yang JY, Zong CS, Xia W, Yamaguchi H, Ding Q, Xie X, Lang JY, Lai CC, Chang CJ, Huang WC, Huang H, Kuo HP, Lee DF, Li LY, Lien HC, Cheng X, Chang KJ, Hsiao CD, Tsai FJ, Tsai CH, Sahin AA, Muller WJ, Mills GB, Yu D, Hortobagyi GN, Hung MC
Affiliation:
Journal:
Nature cell biology

Abstract

The RAS-ERK pathway is known to play a pivotal role in differentiation, proliferation and tumour progression. Here, we show that Erk downregulates Forkhead box O 3a (FOXO3a) by directly interacting with and phosphorylating FOXO3a at Ser 294, Ser 344 and Ser 425, which consequently promotes cell proliferation and tumorigenesis. The ERK-phosphorylated FOXO3a degrades via an MDM2-mediated ubiquitin-proteasome pathway. However, the non-phosphorylated FOXO3a mutant is resistant to the interaction and degradation by murine double minute 2 (MDM2), thereby resulting in a strong inhibition of cell proliferation and tumorigenicity. Taken together, our study elucidates a novel pathway in cell growth and tumorigenesis through negative regulation of FOXO3a by RAS-ERK and MDM2.

  1. Welcome

    Welcome to NIF. Explore available research resources: data, tools and materials, from across the web

  2. Community Resources

    Search for resources specially selected for NIF community

  3. More Resources

    Search across hundreds of additional biomedical databases

  4. Literature

    Search Pub Med abstracts and full text from PubMed Central

  5. Insert your Query

    Enter your search terms here and hit return. Search results for the selected tab will be returned.

  6. Join the Community

    Click here to login or register and join this community.

  7. Categories

    Narrow your search by selecting a category. For additional help in searching, view our tutorials.

  8. Query Info

    Displays the total number of search results. Provides additional information on search terms, e.g., automated query expansions, and any included categories or facets. Expansions, filters and facets can be removed by clicking on the X. Clicking on the + restores them.

  9. Search Results

    Displays individual records and a brief description. Click on the icons below each record to explore additional display options.

X