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. Author manuscript; available in PMC: 2015 Nov 3.
Published in final edited form as: Curr Alzheimer Res. 2015;12(9):847–859. doi: 10.2174/156720501209151019105834

Figure 11. Model of proposed mechanism for the elevation of APP mRNA in ABCA2-overexpressing N2a cells.

Figure 11

ABCA2 overexpression reduces the in vivo binding of JDP2 and HDAC3 at the AP-1 site in the APP promoter, which decreases formation of a transcription repressor complex. APP transcription is positively regulated in ABCA2 overexpressing cells by increased in vivo binding of the c-jun transcriptional activator at the AP-1 site, as well as by the increased in vivo binding of the USF-1 and USF-2 transcriptional activators at the E-box site. APP transcriptional regulation is mediated through PKC. ABCA2 overexpression increases the activity of alkaline and acidic ceramidase enzymes as well as the mass of sphingosine, which is a physiological inhibitor of PKC. Ceramidase inhibition with ceranib-1 or PKC activation with PMA or DAG decreases APP transcription, while inhibition of PKC with GF109203x elevates APP transcription.