title: Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection.
abstract: Prions are composed of an isoform of a normal sialoglycoprotein called PrP(c), whose physiological role has been under investigation, with focus on the screening for ligands. Our group described a membrane 66 kDa PrP(c)-binding protein with the aid of antibodies against a peptide deduced by complementary hydropathy. Using these antibodies in western blots from two-dimensional protein gels followed by sequencing the specific spot, we have now identified the molecule as stress-inducible protein 1 (STI1). We show that this protein is also found at the cell membrane besides the cytoplasm. Both proteins interact in a specific and high affinity manner with a K(d) of 10(-7) M. The interaction sites were mapped to amino acids 113-128 from PrP(c) and 230-245 from STI1. Cell surface binding and pull-down experiments showed that recombinant PrP(c) binds to cellular STI1, and co-immunoprecipitation assays strongly suggest that both proteins are associated in vivo. Moreover, PrP(c) interaction with either STI1 or with the peptide we found that represents the binding domain in STI1 induce neuroprotective signals that rescue cells from apoptosis.
authors.affiliation: Ludwig Institute for Cancer Research, São Paulo Branch, Rua Prof. Antônio Prudente 109 4A, São Paulo 01509010, Brasil.
authors.forename: Silvio M
authors.initials: SM
authors.lastname: Zanata
authors.forename: Marilene H
authors.initials: MH
authors.lastname: Lopes
authors.forename: Adriana F
authors.initials: AF
authors.lastname: Mercadante
authors.forename: Glaucia N M
authors.initials: GN
authors.lastname: Hajj
authors.forename: Luciana B
authors.initials: LB
authors.lastname: Chiarini
authors.forename: Regina
authors.initials: R
authors.lastname: Nomizo
authors.forename: Adriana R O
authors.initials: AR
authors.lastname: Freitas
authors.forename: Ana L B
authors.initials: AL
authors.lastname: Cabral
authors.forename: Kil S
authors.initials: KS
authors.lastname: Lee
authors.forename: Maria A
authors.initials: MA
authors.lastname: Juliano
authors.forename: Elizabeth
authors.initials: E
authors.lastname: de Oliveira
authors.forename: Saul G
authors.initials: SG
authors.lastname: Jachieri
authors.forename: Alma
authors.initials: A
authors.lastname: Burlingame
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Rafael
authors.initials: R
authors.lastname: Linden
authors.forename: Ricardo R
authors.initials: RR
authors.lastname: Brentani
authors.forename: Vilma R
authors.initials: VR
authors.lastname: Martins
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D003300:Copper / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005136:Eye Proteins / Q000737:chemistry / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D007797:Laminin / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000378:metabolism; D018621:PrPC Proteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects; D015398:Signal Transduction
chemical_list: D005136:Eye Proteins; D006360:Heat-Shock Proteins; D007797:Laminin; D046911:Macromolecular Substances; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D018621:PrPC Proteins; D011993:Recombinant Fusion Proteins; C489791:Stip1 protein, mouse; D000841:Anisomycin; D003300:Copper; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases