Tau and GSK3[beta] Dephosphorylations are Required for Regulating Pin1 Phosphorylation

• Published in: Neurochemical research Vol. 30; no. 8; p. 955
• Main Authors: Min, Sae H, Cho, Jung S, Oh, Jae H, Shim, Sun B, Hwang, Dae Y, Lee, Su H, Jee, Seung W, Lim, Hwa J, Kim, Min Y, Sheen, Yhun Y, Lee, Seok H, Kim, Yong K
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01-08-2005
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-005-6177-0

Pin1 binds mitotically phosphorylated Thr231-Pro232 and Thr212-Pro213 sites on tau, and a Pin1 deficiency in mice leads to tau hyperphosphorylation. The aim of this study was to determine if the dephosphorylation or inhibition of tau and GSK3[beta] phosphorylation induces the Pin1 phosphorylation. To test this, human SK-N-MC cells were stably transfected with a fusion gene containing neuron-specific enolase (NSE)-controlled APPsw gene(NSE/APPsw), to induce A[beta]-42. The stable transfectants were then transiently transfected with NSE/Splice, lacking human tau (NSE/Splice), or NSE/hTau, containing human tau, into the cells. The NSE/Splice- and NSE/hTau-cells were then treated with lithium. We concluded that (i) there was more C99-[beta] APP accumulation than C83-[beta]APP in APPsw-tansfectant and thereby promoted A[beta]-42 production in transfectants. (ii) the inhibition of tau and GSK3[beta] phosphorylations correlated with increase in Pin1 activation in NSE/hTau- cells. Thus, these observations suggest that Pin1 might have an inhibitive role in phosphorylating tau and GSK3[beta] for protecting against Alzheimer's disease.