TAp73alpha 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 TAp73alpha 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, DeltaNp73, nor a transcriptionally inactive mutant TAp73alpha(R292H) altered tau phosphorylation indicating that tau phosphorylation is dependent on the transcriptional activity of TAp73alpha. Consistent with this, confocal microscopy revealed that tau and TAp73alpha were spatially separated within the cell; tau being located in the cytoskeletal compartment whilst TAp73alpha 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.
King's College London, MRC Centre for Neurodegenerative Research, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.
Claudie
C
Hooper
Richard
R
Killick
Mahvash
M
Tavassoli
Gerry
G
Melino
Simon
S
Lovestone
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002451:Cell Compartmentation / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D018613:Microscopy, Confocal; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human; D016875:tau Proteins