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 so urce of the 39-43-amino acid beta-amyloid (A beta) peptides that compr ise diffuse and fibrillar deposits in the cerebral cortex and vasculat ure of Alzheimer's disease brains. A beta is thought to play a role in the pathogenesis of Alzheimer's disease, and, hence, considerable eff ort has been invested in defining the means by which A beta is generat ed 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 la rge extracellular amino terminal domain, a single transmembrane segmen t, 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 wit h its cytoplasmic domain. Here, we report the cloning of a cDNA encodi ng one such protein. This ubiquitously expressed 59-kDa APP-binding pr otein, called APP-BP1, is 61% similar to a protein encoded by the Arab idopsis AXR1 gene, required for normal response to the hormone auxin, and is a relative of the ubiquitin activating enzyme E1.