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AC3-33, a novel secretory protein, inhibits Elk1 transcriptional activity via ERK pathway

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Abstract

The transcription factor AP-1 plays an important role in cellular proliferation, transformation and death. In this study, we report a novel human gene, AC3-33 (GenBank name: c3orf33, FLJ31139), which encodes a secretory protein that can inhibit Elk1 transcriptional activity via ERK1/2 pathway. The AC3-33 mRNA encodes a protein of 251 amino acids, which is a classical secretory protein. Functional investigation reveals that overexpression of AC3-33 significantly inhibit AP-1 activity and DNA-binding ability. Further investigation indicated that overexpression of AC3-33 significantly inhibit transcriptional activity of Elk1 and c-jun, but not c-fos. As for the upstream of signaling pathway of Elk-1, our study demonstrated that overexpression of AC3-33 significantly down-regulates phosphorylation of ERK1/2, but not JNK/SAPK or p38 MAPK. These results clearly indicate that AC3-33 is a novel member of the secretory family and inhibits Elk1 transcriptional activity via ERK1/2 MAPK.

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Abbreviations

MAPK:

Mitogen-activated protein kinase

MAPKK, MKK or MEK:

MAPK kinase

MEKK:

MAPKK kinase or MEK kinase

PMA:

Phorbolmyrlstate acetate

AP-1:

Activation protein 1

DMEM:

Dulbecco’s modified Eagle’s medium

ERK:

Extracellular signal regulated protein kinase

Elk1:

The ETS-domain transcription factor

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (30671092), the National High Technology Research and Development Program (863 Program) of China (2006AA02A305), the Natural Science Foundation of Hebei Province (C2009001260), the Central Public-Interest Scientific Institution Basal Research Fund (2009GJSSJKB03), and the Key National S&T Program—“Major New Drug Development” (2009ZX09503-004).

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Authors and Affiliations

  1. Department of Biology, Northchina Coal Medical College, No. 57 JianShe South Road, Tangshan, 063000, People’s Republic of China

    Dongxia Hao, Peng Liu, Jie Zhao, Yang Wang, Wenping Yang & Xiujun Zhang

  2. Chinese National Human Genome Center, No. 3-707 North YongChang Road BDA, Beijing, 100176, People’s Republic of China

    Dongxia Hao, Peng Gao, Yang Lu & Taiping Shi

  3. National Research Institute for Family Planning, No. 12 Da Hui Si Road, Hai Dian District, Beijing, 100081, People’s Republic of China

    Xiujun Zhang

Authors
  1. Dongxia Hao
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  2. Peng Gao
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  3. Peng Liu
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  4. Jie Zhao
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  5. Yang Wang
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  6. Wenping Yang
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  7. Yang Lu
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  8. Taiping Shi
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  9. Xiujun Zhang
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Corresponding authors

Correspondence to Taiping Shi or Xiujun Zhang.

Additional information

Dongxia Hao, Peng Gao contributed equally to this work.

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Hao, D., Gao, P., Liu, P. et al. AC3-33, a novel secretory protein, inhibits Elk1 transcriptional activity via ERK pathway. Mol Biol Rep 38, 1375–1382 (2011). https://doi.org/10.1007/s11033-010-0240-x

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  • DOI: https://doi.org/10.1007/s11033-010-0240-x

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