Microtubule-associated protein tau is a substrate of ATP/Mg(2+)-dependent proteasome protease system
Abstract
Deposition of hyperphosphorylated microtubule-associated protein tau is a recognized pathological process in Alzheimer's disease (AD) brain, however, the mechanism leading to tau accumulation is still not understood. In the present study, we found that different forms of tau, including phosphorylated tau (PHF-1) and non-phosphorylated tau (Tau-1) as well as total tau (Tau-5) in rat brain cortex extract, were degraded when it was co-incubated with ATP and MgCl(2) at 33 degrees C in vitro, and non-phosphorylated tau at Tau-1 epitope was more accessible to the ATP/Mg(2+)-depended proteolysis. With the increase of ATP and MgCl(2) concentration from 5 mM to 20 mM, increased degradation of tau was observed. ATP/Mg(2+)-induced degradation of tau was blocked by lactacystin, a specific proteasome inhibitor and was enhanced by sodium dodecyl sulphate (SDS), a commonly used in vitro proteasome activator, and polyubiquitinated tau with high molecular weight was detected in the presence of lactacystin. Hyperphosphorylated tau isolated from AD brain (AD p-tau) was also partially degraded when it was incubated with rat brain cortex extract in the present of ATP/Mg(2+), and the degradation of AD p-tau was also enhanced by SDS and was inhibited...Continue Reading
Citations
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