title: Identification of candidate proteins binding to prion protein.
abstract: Prion diseases are disorders of protein conformation that produce neurodegeneration in humans and animals. Studies of transgenic (Tg) mice indicate that a factor designated protein X is involved in the conversion of the normal cellular prion protein (PrPC) into the scrapie isoform (PrPSc); protein X appears to interact with PrPC but not with PrPSc. To search for PrPC binding proteins, we fused PrP with alkaline phosphatase (AP) to produce a soluble, secreted probe. PrP-AP was used to screen a lambdagt11 mouse brain cDNA library, and six clones were isolated. Four cDNAs are novel while two clones are fragments of Nrf2 (NF-E2 related factor 2) transcription factor and Aplp1 (amyloid precursor-like protein 1). The observation that PrP binds to a member of the APP (amyloid precursor protein) gene family is intriguing, in light of possible relevance to Alzheimer's disease. Four of the isolated clones are expressed preferentially in the mouse brain and encode a similar motif.
authors.affiliation: Department of Neurology, University of California, San Francisco, California, 94143, USA.
authors.forename: F
authors.initials: F
authors.lastname: Yehiely
authors.forename: P
authors.initials: P
authors.lastname: Bamborough
authors.forename: M
authors.initials: M
authors.lastname: Da Costa
authors.forename: B J
authors.initials: BJ
authors.lastname: Perry
authors.forename: G
authors.initials: G
authors.lastname: Thinakaran
authors.forename: F E
authors.initials: FE
authors.lastname: Cohen
authors.forename: G A
authors.initials: GA
authors.lastname: Carlson
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012608:Scrapie / Q000378:metabolism; D016324:Sequence Tagged Sites; D012995:Solubility
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D011328:Prions; D012313:RNA