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

Regulation of telomerase activity and anti-apoptotic function by protein-protein interaction and phosphorylation.

Authors:
Haendeler J, Hoffmann J, Rahman S, Zeiher AM, Dimmeler S
Affiliation:
Journal:
FEBS letters

Abstract

The enzyme telomerase is necessary for the synthesis and maintenance of telomere length. The catalytic subunit, telomerase reverse transcriptase (TERT), is regulated by interaction with the 90 kDa heat shock protein (HSP90) and by Akt-dependent phosphorylation. Here, we demonstrate that HSP90 and Akt physically interact with TERT. Treatment of cells with novobiocin, which blocks C-terminal interaction of HSP90, disrupted HSP90 binding to Akt, induced Akt dephosphorylation and significantly reduced telomerase activity. The reduction of TERT activity by novobiocin was associated with an increase in apoptosis. Likewise, the induction of Akt dephosphorylation by protein phosphatase 2A (PP2A) reduced telomerase activity. HSP90 is known to prevent PP2A-mediated dephosphorylation of Akt. To investigate whether the effect of novobiocin is due to the reduction of Akt or TERT phosphorylation, we overexpressed a phospho-mimetic, active Akt (T308D/S473D). Akt (T308D/S473D) prevented novobiocin-induced reduction of telomerase activity and the stimulation of apoptosis. Moreover, overexpression of a dominant negative PP2A construct (PP2A(L199P)) as well as incubation with the PP2A inhibitor okadaic acid blocked the inhibition of telomerase activity by novobiocin. These data suggest that the association between HSP90, Akt and TERT in concert with the phosphorylation of TERT is necessary for maintaining telomerase activity and inhibition of apoptosis.

  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