APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein.
beta-Amyloid protein precursors (APPs, 695-770 amino acids) are the source of the 39-43 amino acid beta-amyloid (A beta) peptides that comprise diffuse and fibrillar deposits in the cerebral cortex and vasculature of Alzheimer's disease brains. A beta is thought to play a role in the pathogenesis of Alzheimer's disease, and, hence, considerable effort has been invested in defining the means by which A beta is generated from the APPs. Knowledge of the normal function of the APPs is sure to provide insights into the genesis and pathological persistence of A beta in Alzheimer's disease. APP is a cell surface protein with a large extracellular amino-terminal domain, a single transmembrane segment, and a short cytoplasmic tail. Its location and structural features characteristic of a receptor for signal transduction led us to search for potential effector proteins capable of binding and interacting with its cytoplasmic domain. Here, we report the cloning of a cDNA encoding one such protein. This ubiquitously expressed 59-kDa APP-binding protein, called APP-BP1, is 61% similar to a protein encoded by the Arabidopsis AXR1 gene, required for normal response to the hormone auxin, and is a relative of the ubiquitin activating enzyme E1.
Chow
N
N
Molecular Neurogenetics Laboratory, McLean Hospital, Belmont, Massachusetts 02178, USA.
Korenberg
J R
JR
Chen
X N
XN
Neve
R L
RL
D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D005333:Fetus; D015723:Gene Library; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014908:Triticum; D044764:Ubiquitin-Activating Enzymes
D016564:Amyloid beta-Protein Precursor; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D044764:Ubiquitin-Activating Enzymes; C491802:NAE protein, human