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


Role of APP phosphorylation in FE65-dependent gene transactivation mediated by AICD.

Nakaya T, Suzuki T
Genes to cells : devoted to molecular & cellular mechanisms


Consecutive cleavages of Alzheimer's amyloid beta-protein precursor (APP) generate intracellular domain fragment (AICD). Interaction of APP and/or AICD with the adaptor protein FE65 is thought to modulate the metabolism of APP and the function of AICD. Phosphorylation or amino acid substitution of APP and AICD at threonine 668 (Thr668) suppresses their association with FE65. Here, we analyzed the function of APP and AICD phosphorylation in the nuclear translocation of FE65. In brain, AICD was present as phosphorylated and non-phosphorylated forms with non-phosphorylated AICD being dominantly detected in the nucleus. However, a mutant AICD (AICDa), in which Thr668 of AICD was replaced with Ala, was also mostly localized to the nucleus. These observations indicate that phosphorylation of AICD does not regulate the translocation of FE65 and that FE65 does not accompany AICD into the nucleus. APP was known to tether FE65 to the membrane. We found that phosphorylation of APP liberated membrane-bound FE65, which was then translocated into the nucleus where it up-regulated gene transactivation mediated by AICD, which was translocated into the nucleus independently of FE65. Therefore, phosphorylation of APP but not AICD modulates FE65-dependent gene transactivation mediated by AICD through the regulation of FE65 intracellular localization.

  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.