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The AICD Interacting Protein DAB1 is Up-Regulated in Alzheimer Frontal Cortex Brain Samples and Causes Deregulation of Proteins Involved in Gene Expression Changes

[ Vol. 8 , Issue. 5 ]

Author(s):

T. Muller, C. Loosse, A. Schrotter, A. Schnabel, S. Helling, R. Egensperger and K. Marcus   Pages 573 - 582 ( 10 )

Abstract:


AICD is the intracellular subdomain of the amyloid precursor protein thought to play a pivotal role as a potential transcription factor that might be of relevance for the pathophysiology of Alzheimers disease. For its signal transduction potential AICD requires interacting proteins like FE65 and TIP60. However, many other proteins were described being able to bind to AICD. Here, we studied mRNA levels of AICD interacting proteins and found one of them (DAB1) strongly up-regulated in human post-mortem frontal cortex brain samples of AD patients. Subsequent cell culture experiments revealed that elevated DAB1 level results in the deregulation of the cellular proteome. We found the proliferation associated protein 2G4 as well as the guanine monophosphate synthetase (GMPS) significantly up-regulated in DAB1 over-expressing cells. Both proteins can be involved in cellular transcription processes supporting the hypothesis that DAB1 acts via modification of the AICD-dependent transcriptionally active complex. Of note, expression of the three components of the putative transcription complex (AICD, FE65, and TIP60 (AFT)) also revealed deregulation of the GMPS protein in an opposite fashion. Our results point to a putative relevance of AICD-dependent mechanisms in AD, caused by protein abundance changes of AICD interacting proteins, as shown for DAB1 in this work.

Keywords:

AICD, APP, DAB1, Alzheimer disease, gene expression, proteomics, transmembrane protein, amyloidogenic plaques, apolipoprotein receptor, cytoplasm, histone acetyltransferase TIP60

Affiliation:

Functional Proteomics, Medizinisches Proteom-Center, Ruhr-University Bochum, D-44780 Bochum, Germany.



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