GSKIP,an inhibitor of GSK3β, mediates the N‐cadherin/β‐catenin pool in the differentiation of SH‐SY5Y cells |
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Authors: | Ching‐Chih Lin Chia‐Hua Chou Shen‐Long Howng Chia‐Yi Hsu Chi‐Ching Hwang Chihuei Wang Ching‐Mei Hsu Yi‐Ren Hong |
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Affiliation: | 1. Department of Biochemistry, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC;2. Department of Biological Sciences, National Sun Yat‐Sen University, Kaohsiung, Taiwan, ROC;3. Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC;4. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC;5. Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC |
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Abstract: | Emerging evidence has shown that GSK3β plays a pivotal role in regulating the specification of axons and dendrites. Our previous study has shown a novel GSK3β interaction protein (GSKIP) able to negatively regulate GSK3β in Wnt signaling pathway. To further characterize how GSKIP functions in neurons, human neuroblastoma SH‐SY5Y cells treated with retinoic acid (RA) to differentiate to neuron‐like cells was used as a model. Overexpression of GSKIP prevents neurite outgrowth in SH‐SY5Y cells. GSKIP may affect GSK3β activity on neurite outgrowth by inhibiting the specific phosphorylation of tau (ser396). GSKIP also increases β‐catenin in the nucleus and raises the level of cyclin D1 to promote cell‐cycle progression in SH‐SY5Y cells. Additionally, overexpression of GSKIP downregulates N‐cadherin expression, resulting in decreased recruitment of β‐catenin. Moreover, depletion of β‐catenin by small interfering RNA, neurite outgrowth is blocked in SH‐SY5Y cells. Altogether, we propose a model to show that GSKIP regulates the functional interplay of the GSK3β/β‐catenin, β‐catenin/cyclin D1, and β‐catenin/N‐cadherin pool during RA signaling in SH‐SY5Y cells. J. Cell. Biochem. 108: 1325–1336, 2009. © 2009 Wiley‐Liss, Inc. |
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Keywords: | Wnt signaling pathway retinoic acid neurite outgrowth cyclin D1 |
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