Research Papers:

Phorbol esters dPPA/dPA promote furin expression involving transcription factor CEBPβ in neuronal cells

Jing-Si Zha, Bing-Lin Zhu, Lu Liu, Yu-Jie Lai, Yan Long, Xiao-Tong Hu, Xiao-Juan Deng, Xue-Feng Wang, Zhen Yan and Guo-Jun Chen _

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Oncotarget. 2017; 8:60159-60172. https://doi.org/10.18632/oncotarget.18569

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Jing-Si Zha1,*, Bing-Lin Zhu1,*, Lu Liu1, Yu-Jie Lai1, Yan Long1, Xiao-Tong Hu1, Xiao-Juan Deng1, Xue-Feng Wang1, Zhen Yan2 and Guo-Jun Chen1

1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China

2Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY, 14214, USA

*These authors contributed equally to this work

Correspondence to:

Guo-Jun Chen, email: [email protected]

Keywords: furin, dPPA/dPA, CEBPβ, ERK, PI3K

Received: December 20, 2016     Accepted: June 10, 2017     Published: June 19, 2017


Using high-throughput small molecule screening targeting furin gene, we identified that phorbol esters dPPA (12-Deoxyphorbol 13-phenylacetate 20-acetate) and dPA (12-Deoxyphorbol 13-acetate) significantly increased furin protein and mRNA expression in SH-SY5Y cells. This effect was prevented by PKC (protein kinase C) inhibitor calphostin C but not Ro318220, suggesting that the C1 domain, rather than the catalytic domain of PKC plays an important role. Luciferase assay revealed that nucleotides -7925 to -7426 were sufficient to mediate dPPA/dPA enhancement of furin P1 promoter activity. RNA interference of transcriptional factors CEBPβ (CCAAT/enhancer-binding protein β) and GATA1 revealed that knockdown of CEBPβ significantly attenuated the effect of dPPA on furin expression. Pharmacological inhibition of ERK and PI3K but not TGFβ receptor diminished the up-regulation of furin by dPPA. These results suggested that in neuronal cells, transcriptional activation of furin by dPPA/dPA may be initiated by C1 domain containing proteins including PKC; the intracellular signaling involves ERK and PI3K and transcription factor CEBPβ.

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