Forgot your Password

If you have forgotten your password, please enter your account email below and we will reset your password and email you the new password.


Login to SciCrunch


Register an Account

Delete Saved Search

Are you sure you want to delete this saved search?


NIF LinkOut Portal


Superoxide anions regulate TORC1 and its ability to bind Fpr1:rapamycin complex.

Neklesa TK, Davis RW
Proceedings of the National Academy of Sciences of the United States of America


The small natural product rapamycin, when bound to FKBP12, is a potent inhibitor of an evolutionarily conserved Target of Rapamycin Complex 1 (TORC1), which plays a central role in mediating cellular response to nutrient availability. Given the prominent role of TORC1 in cell growth and proliferation, clinical trials have explored the possibility of using rapamycin as an anticancer agent. Unfortunately, the percentage of patients responding favorably has been low, intensifying the need to find biomarkers able to predict rapamycin sensitivity or resistance. In this study, we elucidate the molecular mechanism underlying partial rapamycin resistance in yeast. Using the yeast deletion collection, we identified 15 deletion strains leading to partial rapamycin resistance. Among these were Cu/Zn-superoxide dismutase Sod1, copper transporter Ctr1, and copper chaperone Lys7, suggesting a role for oxidative stress in rapamycin resistance. Further analysis revealed that all 15 strains exhibit elevated levels of superoxide anions, and we show that elevated levels of reactive oxygen species specifically modify TORC1 such that it is no longer able to fully bind FKBP12:rapamycin. Therefore, elevated oxidative stress modifies TORC1 and prevents its binding to the FKBP12:rapamycin complex, ultimately leading to rapamycin resistance. These results warrant an examination into whether similar reasons explain rapamycin resistance observed in various clinical samples.

  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.