title: Signaling via amyloid precursor-like proteins APLP1 and APLP2.
abstract: The amyloid-β protein precursor (AβPP) has been implicated in Alzheimer's disease (AD) not only as a precursor of the amyloid-β peptide but also as a mediator of signal transduction. We recently identified novel mediators of AβPP signaling via interactions with Mint/X11 family proteins Mint1 and Mint3. These mediators include transcriptional co-activators Taz and Yap. Here we show that Taz and Yap also mediate signaling via the AβPP paralogues APLP1 and APLP2 through interactions with Mint1 and Mint3. APLP1 and APLP2 formed transcriptionally active triple protein complexes with the adaptor protein Mint3 and each of the transcriptional regulators Taz and Yap, and complex formation was regulated by the γ-secretase cleavage of APLP1 and APLP2. The presence of Mint1 instead of Mint3 in the complex prevented its translocation to the nucleus. APLP1 displayed much lower transactivation levels compared to AβPP and APLP2. These results indicate that all three AβPP family members are capable of activating gene transcription via Mint3-Taz and Mint3-Yap.
authors.affiliation: Buck Institute for Age Research, Novato, CA 94945, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Orcholski
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bredesen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C079091:APBA1 protein, human; C117536:APBA3 protein, human; C489697:APLP1 protein, human; C084104:APLP2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins