Tau dephosphorylation potentiates apoptosis by mechanisms involving a failed dephosphorylation/activation of Bcl-2.
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.
Liu
Xin-An
XA
Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China.
Liao
Kai
K
Liu
Rong
R
Wang
Hai-Hong
HH
Zhang
Yao
Y
Zhang
Qi
Q
Wang
Qun
Q
Li
Hong-Lian
HL
Tian
Qing
Q
Wang
Jian-Zhi
JZ
D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology*; D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019254:Genes, bcl-2 / Q000235:genetics*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D016875:tau Proteins / Q000502:physiology*
D000911:Antibodies, Monoclonal; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases