NIF LinkOut Portal

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

mTORC1 signaling requires proteasomal function and the involvement of CUL4-DDB1 ubiquitin E3 ligase.

Authors:
Ghosh P, Wu M, Zhang H, Sun H
Affiliation:
Journal:
Cell cycle (Georgetown, Tex.)

Abstract

The mammalian target-of-rapamycin (mTOR) signaling pathway serves as a major regulator of cell growth, cell size and metabolism. In vivo, mTOR exists in two complexes, both of which contain the catalytic subunit mTOR, the invariable subunit mLST8, and a complex specific subunit Raptor or Rictor, forming either the rapamycin-sensitive mTORC1 or rapamycin-insensitive mTORC2, respectively. The exact functions of Raptor or Rictor in these complexes are still unclear. Here we demonstrate that mTORC1-mediated signaling events require the function of the 26S proteasome. Inhibition of the 26S proteasome by MG132 leads to the rapid inhibition of phosphorylation of the mTORC1 substrates S6 kinase and 4E-BP1. We have further discovered that the WD40 repeat proteins Raptor and mLST8 bind the CUL4-DDB1 ubiquitin E3 ligase. Loss of CUL4B or DDB1 specifically blocks the phosphorylation of S6 kinase at threonine 389 and 4E-BP1 at serine 65 and threonines 37 and 46, while loss of CUL4B enhances the phosphorylation of AKT at serine 473. These phosphorylation effects are identical to those resulting from the inactivation of Raptor. Our data suggest that the CUL4-DDB1 ubiquitin ligase interacts with Raptor and regulates the mTORC1- mediated signaling pathway through ubiquitin-dependent proteolysis.

  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