title: Tau pathology modulates Pin1 post-translational modifications and may be relevant as biomarker.
abstract: A prerequisite to dephosphorylation at Ser-Pro or Thr-Pro motifs is the isomerization of the imidic peptide bond preceding the proline. The peptidyl-prolyl cis/trans isomerase named Pin1 catalyzes this mechanism. Through isomerization, Pin1 regulates the function of a growing number of targets including the microtubule-associated tau protein and is supposed to be deregulated Alzheimer's disease (AD). Using proteomics, we showed that Pin1 is posttranslationally modified on more than 5 residues, comprising phosphorylation, N-acetylation, and oxidation. Although Pin1 expression remained constant, Pin1 posttranslational two-dimensional pattern was modified by tau overexpression in a tau-inducible neuroblastoma cell line, in our THY-Tau22 mouse model of tauopathy as well as in AD. Interestingly, in all of these systems, Pin1 modifications were very similar. In AD brain tissue when compared with control, Pin1 is hyperphosphorylated at serine 16 and found in the most insoluble hyperphosphorylated tau fraction of AD brain tissue. Furthermore, in all tau pathology conditions, acetylation of Pin1 may also contribute to the differences observed. In conclusion, Pin1 displays several posttranslational modifications, which are specific in tauopathies and may be useful as biomarker.
authors.affiliation: Inserm, UMR 837, Alzheimer & Tauopathies, Jean-Pierre Aubert Research Centre, Faculty of Medicine, Institute of Predictive Medicine and Therapeutic Research, Lille, France.
authors.forename: Kunie
authors.initials: K
authors.lastname: Ando
authors.forename: Pierre
authors.initials: P
authors.lastname: Dourlen
authors.forename: Anne-Véronique
authors.initials: AV
authors.lastname: Sambo
authors.forename: Alexis
authors.initials: A
authors.lastname: Bretteville
authors.forename: Karim
authors.initials: K
authors.lastname: Bélarbi
authors.forename: Valérie
authors.initials: V
authors.lastname: Vingtdeux
authors.forename: Sabiha
authors.initials: S
authors.lastname: Eddarkaoui
authors.forename: Hervé
authors.initials: H
authors.lastname: Drobecq
authors.forename: Antoine
authors.initials: A
authors.lastname: Ghestem
authors.forename: Séverine
authors.initials: S
authors.lastname: Bégard
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Demey-Thomas
authors.forename: Patricia
authors.initials: P
authors.lastname: Melnyk
authors.forename: Caroline
authors.initials: C
authors.lastname: Smet
authors.forename: Guy
authors.initials: G
authors.lastname: Lippens
authors.forename: Claude-Alain
authors.initials: CA
authors.lastname: Maurage
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Caillet-Boudin
authors.forename: Yann
authors.initials: Y
authors.lastname: Verdier
authors.forename: Joelle
authors.initials: J
authors.lastname: Vinh
authors.forename: Isabelle
authors.initials: I
authors.lastname: Landrieu
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Galas
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.forename: Malika
authors.initials: M
authors.lastname: Hamdane
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010084:Oxidation-Reduction; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011392:Proline / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D020543:Proteome; D012694:Serine / Q000378:metabolism; D024801:Tauopathies / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C054369:MAPT protein, human; C558298:Mapt protein, mouse; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D020543:Proteome; D016875:tau Proteins; D012694:Serine; D011392:Proline; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse