APP-BP1, a Novel Protein That Binds to the Carboxyl-terminal Region of the Amyloid Precursor Protein

doi:10.1074/jbc.271.19.11339

APP-BP1, a Novel Protein That Binds to the Carboxyl-terminal Region of the Amyloid Precursor Protein (*)

From the (1)Molecular Neurogenetics Laboratory, McLean Hospital, Belmont, Massachusetts 02178, the
(2)Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, and the
(3)Department of Genetics, Ahmanson Department of Pediatrics, Cedars-Sinai Research Institute, UCLA, Los Angeles, California 92717

^¶ To whom correspondence should be addressed:
202 MRC, McLean Hospital, 115 Mill St., Belmont, MA 02178.
Tel.: 617-855-2413; Fax: 617-855-3793.

↵^§ Current address: Dept. of Neurobiology and Anatomy, Box 603, The University of Rochester, Medical Center, 601 Elmwood Ave., Rochester, NY 14642. Tel.: 716-275-6665; Fax: 716-273-1132.

Abstract

β-Amyloid protein precursors (APPs, 695-770 amino acids) are the source of the 39-43-amino acid β-amyloid (Aβ) peptides that comprise diffuse and fibrillar deposits in the cerebral cortex and vasculature of Alzheimer's disease brains. Aβ 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 Aβ 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 Aβ 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.

Footnotes

↵* This work was supported by National Institutes of Health Grant AG12954 (to R. L. N.) and a Livingston fellowship (to N. W. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(™)/EMBL Data Bank with accession number(s) U50939.
↵¹ The abbreviations used are:

APP

β-amyloid protein precursor

APLP

amyloid precursor-like protein

GST

glutathione S-transferase

PCR

polymerase chain reaction

PBS

phosphate-buffered saline

MBP

maltose-binding protein

PAGE

polyacrylamide gel electrophoresis

bp

base pair(s).
- Received December 26, 1995.
- Revision received February 26, 1996.