TAp73α induces tau phosphorylation in HEK293a cells via a transcription-dependent mechanism

p73 and tau both play roles in neurodevelopment and neurodegeneration. In this pilot study we show by Western blotting that TAp73α induces phosphorylation of human 2N4R tau at threonine-205 and at the PHF-1 epitope (serine366/serine404) in HEK293a cells. Neither the dominant negative isoform, ΔNp73, nor a transcriptionally inactive mutant TAp73αR292H altered tau phosphorylation indicating that tau phosphorylation is dependent on the transcriptional activity of TAp73α. Consistent with this, confocal microscopy revealed that tau and TAp73α were spatially separated within the cell; tau being located in the cytoskeletal compartment whilst TAp73α was found in the nucleus. These findings have ramifications for microtubule dynamics associated with axonal growth during development and for neuronal death associated with Alzheimer's disease and other tauopathies.