p53 is upregulated in Alzheimer's disease and induces tau phosphorylation in HEK293a cells.
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.
Hooper
Claudie
C
King's College London, MRC Centre for Neurodegenerative Research, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.
Meimaridou
Eirini
E
Tavassoli
Mahvash
M
Melino
Gerry
G
Lovestone
Simon
S
Killick
Richard
R
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D018613:Microscopy, Confocal; D010766:Phosphorylation; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D016875:tau Proteins