Nuclear signaling: a common function of presenilin substrates?
Major progress has recently been made in the characterization of the secretases involved in endoproteolytic processing of the Alzheimer's disease (AD)-associated beta-amyloid precursor protein, betaAPP. betaAPP is the precursor of the amyloid beta-peptide, which is a major constituent of amyloid plaques in the brains of Alzheimer patients. It is now commonly believed that Abeta plays a pivotal role in the pathogenesis of AD, and that inhibiting the production of Abeta may help to treat or to prevent the disease. With beta-secretase and the presenilins, two essential factors in the proteolytic generation of Abeta have now been identified. However, very little is still known about the biological function of the long-known betaAPP. In this review we will discuss a novel putative function of betaAPP in nuclear signaling, an activity, that betaAPP may share with other presenilin substrates such as Notch.
Steiner
H
H
Adolf-Butenandt-lnstitute, Department of Biochemistry, Ludwig-Maximilians-University, Munich, Germany. hsteiner@pbm.med.uni-muenchen.de
Haass
C
C
D000123:Acetyltransferases / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D051548:Histone Acetyltransferases; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D053764:Presenilin-1; D017434:Protein Structure, Tertiary / Q000502:physiology; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors
C091042:APBB1 protein, human; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5