Tau dephosphorylation potentiates apoptosis by mechanisms involving a failed dephosphorylation/activation of Bcl-2

Xin An Liu, Kai Liao, Rong Liu, Hai Hong Wang, Yao Zhang, Qi Zhang, Qun Wang, Hong Lian Li, Qing Tian, Jian Zhi Wang

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Phosphorylation of tau, a major microtubule-associated protein, has been recently discovered to affect cell apoptosis. While the phosphorylation of tau is dynamically regulated, the role of tau dephosphorylation in cell viability is elusive. Here, we observed that the cells bearing high level of the dephosphorylated tau at Tau-1 epitope were more vulnerable to the apoptosis induced by staurosporine, camptothecin, and hydrogen peroxide, though the general outcome of tau expression was still anti-apoptotic. Further studies demonstrate that co-expression of tau and protein phosphatase 2A catalytic subunit (PP2Ac), the most active tau phosphatase, potentiates cell apoptosis with a correlatively increased dephosphorylation of tau and phosphorylation of Bcl-2 at Ser87 (pS87-Bcl2, the inactive form of the anti-apoptotic factor), whereas expression of PP2Ac alone in the absence of tau decreases the levels of pS87-Bcl2 and cleaved PARP, markers of early apoptosis. Finally, both tau and Bcl-2 were co-immunoprecipitated with PP2Ac, but the binding level of Bcl-2 with PP2Ac decreased prominently when tau was co-expressed. These data suggest that tau dephosphorylation by PP2Ac facilitates cell apoptosis with the mechanisms involving a failed dephosphorylation/activation of Bcl-2.

Original languageEnglish
Pages (from-to)953-962
Number of pages10
JournalJournal of Alzheimer's Disease
Volume19
Issue number3
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-2
  • Protein phosphatase
  • Tau phosphorylation

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