Work

P44, the ‘longevity‐assurance’ isoform of P53, regulates tau phosphorylation and is activated in an age‐dependent fashion

Year: 2013

Type: article

Abstract: p44 is a short isoform of p53 with 'longevity-assurance' activity. Overexpression of p44 in the mouse (p44(+/+) transgenic mice) causes a progeroid phenotype that mimics an accelerated form of aging. The phenotype includes abnormal phosphorylation of the microtubule-binding protein tau, synaptic deficits, and cognitive decline. Genetic engineering demonstrated that the phosphorylation status of tau acts upstream of the synaptic deficits. Here, we provide evidence that p44 promotes the phosphorylation of tau in the mouse. Specifically, we show that p44 binds to the promoter of tau kinases Dyrk1A, GSK3β, Cdk5, p35, and p39 and activates their transcription. The upregulation of the above kinases is followed by increased phosphorylation of tau. Finally, we show that p44 is preferentially found in the nucleus and that its levels increase with age in the mouse brain. Taken together, these results suggest that an imbalance in the p53:p44 ratio might be involved with the altered tau metabolism that characterizes aging.

Source: Aging Cell

DOI: 10.1111/acel.12192

Authors: Mariana Pehar, Mi Hee Ko, Mi Li, Heidi Scrable, Luigi Puglielli

Institutions: University of Wisconsin–Madison, Mayo Clinic, William S. Middleton Memorial Veterans Hospital

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,790