p53 is upregulated in Alzheimer's disease and induces tau phosphorylation in HEK293a cells

• Published in: Neuroscience letters Vol. 418; no. 1; pp. 34 - 37
• Main Authors: Hooper, Claudie, Meimaridou, Eirini, Tavassoli, Mahvash, Melino, Gerry, Lovestone, Simon, Killick, Richard
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 11.05.2007; Elsevier; Elsevier Scientific Publishers Ireland
• Subjects: Aged; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Humans; Medical sciences; Microscopy, Confocal; Microtubules; Neurology; p53; Phosphorylation; Tau; tau Proteins - metabolism; Temporal Lobe - metabolism; Temporal Lobe - pathology; Tumor Suppressor Protein p53 - metabolism; Vertebrates: nervous system and sense organs; Tau; Alzheimer's disease; Microtubules; p53; Nervous system diseases; Phosphorylation; Alzheimer disease; p53 Protein; Cerebral disorder; Tau protein; Central nervous system disease; Cytoskeleton; Degenerative disease; Microtubule
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2007.03.026

p53 and tau are both associated with neurodegenerative disorders. Here, we show by Western blotting that p53 is upregulated approximately 2-fold in the superior temporal gyrus of Alzheimer's patients compared to healthy elderly control subjects. Moreover, p53 was found to induce phosphorylation of human 2N4R tau at the tau-1/AT8 epitope in HEK293a cells. Confocal microscopy revealed that tau and p53 were spatially separated intracellularly. Tau was found in the cytoskeletal compartment, whilst p53 was located in the nucleus, indicating that the effects of p53 on tau phosphorylation are indirect. Collectively, these findings have ramifications for neuronal death associated with Alzheimer's disease and other tauopathies.