title: Identification of a mutant-like conformation of p53 in fibroblasts from sporadic Alzheimer's disease patients.
abstract: Here we show that fibroblasts from sporadic Alzheimer's disease (AD) patients specifically express an anomalous and detectable conformational state of p53 that makes these cells distinct from fibroblasts of age-matched non-AD subjects. In particular, we found that, in contrast to non-AD fibroblasts, p53 in AD fibroblasts is expressed at higher levels in resting condition, and presents a significant impairment of its DNA binding and transcriptional activity. All together, these findings figured out the presence of a mutant-like p53 phenotype. However, gene sequencing of the entire p53 gene from either AD or non-AD did not unravel point mutations. Based on immunoprecipitation studies with conformation-specific p53 antibodies (PAb1620 and PAb240), which discriminated folded versus unfolded p53 tertiary structure, we found that a significant amount of p53 assumed an unfolded tertiary structure in fibroblasts from AD patients. This conformational mutant-like p53 form was virtually undetectable in fibroblasts from non-AD patients. These data, independently from their relevance in understanding the etiopathogenesis of AD, might be useful for supporting AD diagnosis.
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, University of Brescia, Viale Europa 11, 25124 Brescia, Italy. uberti@med.unibs.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Uberti
authors.forename: Cristina
authors.initials: C
authors.lastname: Lanni
authors.forename: Teresina
authors.initials: T
authors.lastname: Carsana
authors.forename: Simona
authors.initials: S
authors.lastname: Francisconi
authors.forename: Cristina
authors.initials: C
authors.lastname: Missale
authors.forename: Marco
authors.initials: M
authors.lastname: Racchi
authors.forename: Stefano
authors.initials: S
authors.lastname: Govoni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Memo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D004252:DNA Mutational Analysis / Q000379:methods; D004317:Doxorubicin / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D009154:Mutation; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D002945:Cisplatin