Cellular and Molecular Life Sciences

, Volume 66, Issue 13, pp 2181–2193

Calcium signaling-induced Smad3 nuclear accumulation induces acetylcholinesterase transcription in apoptotic HeLa cells

Research Article


Recently, acetylcholinesterase (AChE) has been studied as an important apoptosis regulator. We previously showed that cellular calcium mobilization upregulated AChE expression by modulating promoter activity and mRNA stability. In this study, we have identified a potential Smad3/4 binding element, TGCCAGACA, located within the −601 to −571 bp fragment of the AChE promoter, as an important calcium response motif. Smad2/3 and Smad4 were shown to bind this element. Overexpression of human Smad3 increased AChE transcription activity in a dose-dependent manner in HeLa cells, whereas dominant-negative Smad3 blocked this activation. Upon A23187 and thapsigargin treatment, nuclear Smad3 accumulation was observed, an effect that was blocked by the intracellular Ca2+ chelator BAPTA–AM. Calcium-induced AChE transcriptional activation was significantly blocked when the nuclear localization signal of Smad3 was destroyed. Taken together, our data suggest Smad3 can regulate AChE transcriptional activation following calcium-induced nuclear accumulation.


Smad3 Acetylcholinesterase Cellular calcium perturbation Apoptosis Nuclear accumulation Transcriptional activation 


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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Wei Gao
    • 1
  • Hui Zhu
    • 1
  • Jing-Ya Zhang
    • 1
  • Xue-Jun Zhang
    • 1
  1. 1.Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina

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