  Cells are constantly exposed to DNA damaging insults. To protect the
organism, cells developed a complex molecular response coordinated by P53, the
master regulator of DNA repair, cell division and cell fate. DNA damage
accumulation and abnormal cell fate decision may represent a pathomechanism
shared by aging-associated disorders such as cancer and neurodegeneration.
Here, we examined this hypothesis in the context of tauopathies, a
neurodegenerative disorder group characterized by Tau protein deposition. For
this, the response to an acute DNA damage was studied in neuroblastoma cells
with depleted Tau, as a model of loss-of-function. Under these conditions,
altered P53 stability and activity result in reduced cell death and increased
cell senescence. This newly discovered function of Tau involves abnormal
modification of P53 and its E3 ubiquitin ligase MDM2. Considering the medical
need with vast social implications caused by neurodegeneration and cancer, our
study may reform our approach to disease-modifying therapies.
