Tau pathology modulates Pin1 post-translational modifications and may be relevant as biomarker |
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Authors: | Kunie Ando Pierre Dourlen Anne-Véronique Sambo Alexis Bretteville Karim Bélarbi Valérie Vingtdeux Sabiha Eddarkaoui Hervé Drobecq Antoine Ghestem Séverine Bégard Emmanuelle Demey-Thomas Patricia Melnyk Caroline Smet Guy Lippens Claude-Alain Maurage Marie-Laure Caillet-Boudin Yann Verdier Joelle Vinh Isabelle Landrieu Marie-Christine Galas David Blum Malika Hamdane Nicolas Sergeant Luc Buée |
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Institution: | 1. Inserm, UMR 837, Alzheimer & Tauopathies, Jean-Pierre Aubert Research Centre, Faculty of Medicine, Institute of Predictive Medicine and Therapeutic Research, Lille, France;2. Univ. Lille Nord de France, UDSL, Lille, France;3. CNRS, UMR 8161, Institut Pasteur de Lille, Lille, France;4. ESPCI Biological Mass Spectrometry and Proteomics USR 3149 CNRS/ESPCI ParisTech, Paris, France;5. CNRS, UMR 8576, Univ Lille1, Villeneuve d''Ascq, France;6. CHR-Lille, Department of anatomo-pathology, Lille, France |
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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. |
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Keywords: | Alzheimer's disease Tauopathy Pin1 Microtubule-associated protein tau Proteomics Phosphorylation Acetylation Posttranslational modification Biomarker |
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