A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein

Takuo Watanabe, Jun Sukegawa, Izumi Sukegawa, Susumu Tomita, Ko Ichi Iijima, Shinobu Oguchi, Toshiharu Suzuki, Angus C. Nairn, Paul Greengard

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Alzheimer amyloid precursor protein (APP) is an integral membrane protein with a short cytoplasmic domain of 47 amino acids. It is hoped that identification of proteins that interact with the cytoplasmic domain will provide new insights into the physiological function of APP and, in turn, into the pathogenesis of Alzheimer's disease. To identify proteins that interact with the cytoplasmic domain of APP, we employed affinity chromatography using an immobilized synthetic peptide corresponding to residues 645-694 of APP695 and identified a protein of ~130 kDa in rat brain cytosol. Amino acid sequencing of the protein revealed the protein to be a rat homologue of monkey UV-DDB (UV-damaged DNA-binding protein, calculated molecular mass of 127 kDa). UV-DDB/p127 co-immunoprecipitated with APP using an anti-APP antibody from PC12 cell lysates. APP also coimmunoprecipitated with UV-DDB/p127 using an anti-UV-DDB/p127 antibody. These results indicate that UVDDB/p127, which is present in the cytosolic fraction, forms a complex with APP through its cytoplasmic domain. In vitro binding experiments using a glutathione S-transferase-APP cytoplasmic domain fusion protein and several mutants indicated that the YENPTY motif within the APP cytoplasmic domain, which is important in the internalization of APP and amyloid β protein secretion, may be involved in the interaction between UV- DDB/p127 and APP.

Original languageEnglish
Pages (from-to)549-556
Number of pages8
JournalJournal of Neurochemistry
Volume72
Issue number2
DOIs
Publication statusPublished - 1999

Keywords

  • Amyloid precursor protein
  • DNA repair
  • UV-damaged DNA binding protein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein'. Together they form a unique fingerprint.

Cite this