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The expression of antiapoptotic protein survivin is transcriptionally upregulated by DEC1 primarily through multiple sp1 binding sites in the proximal promoter

Oncogene volume 25, pages 3296–3306 (2006)Cite this article

Abstract

Human differentially expressed in chondrocytes (DEC), mouse stimulated with retinoic acid and rat split and hairy related proteins constitute a structurally distinct class of the basic helix-loop-helix proteins. DEC1 is abundantly expressed in tumors and protects against apoptosis induced by serum starvation. In this study, we report that DEC1 antiapoptosis is achieved by inducing survivin, an antiapoptotic protein. In paired tumor–normal tissues, survivin and DEC1 exhibited a paralleled expression pattern. Tetracycline-induced expression of DEC1 in stable lines proportionally increased the expression of survivin. In reporter assays, DEC1 transactivated the survivin promoter but repressed the DEC2 promoter. In contrast to the repression, the activation was delayed and varied depending on serum concentrations and cycle blockers. Studies with reporter mutants located, in the survivin promoter, two Sp1 sites that supported DEC1 transactivation. Electrophoretic mobility shift assay and chromatin immunoprecipitation detected the presence of DEC1 in the survivin promoter. These findings establish that the survivin gene is a transcription target of DEC1, and induction of survivin is at least in part responsible for DEC1 antiapoptosis.

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Abbreviations

bHLH:

basic helix-loop-helix

ChIP:

chromatin immunoprecipitation

DEC:

differentially expressed in chondrocytes

DMEM:

Dulbecco's modified Eagle's medium

DTT:

dithiothreitol

EMSA:

electrophoretic mobility shift assay

HLH:

helix-loop-helix

IAP:

inhibitor of apoptosis

PCR:

polymerase chain reaction

PBS:

phosphate-buffered saline

RT–PCR:

reverse transcription-polymerase chain reaction

SDS–PAGE:

sodium dodecyl sulfate–polyacrylamide gel electrophoresis

SHARP:

split and hairy related protein

STRA:

stimulated with retinoic acid.

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Acknowledgements

We thank Dr Fengzhi Li for providing the pSurvivin-6270 reporter. This work was partially supported by National Institutes of Health Grants R01ES07965, R01GM61988 and F05AT003019 (to BY).

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Authors and Affiliations

  1. Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA

    Y Li, M Xie, J Yang, D Yang, R Deng & B Yan

  2. Department of Biology, Providence College, Providence, RI 02908, USA

    Y Wan

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Correspondence to B Yan.

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Li, Y., Xie, M., Yang, J. et al. The expression of antiapoptotic protein survivin is transcriptionally upregulated by DEC1 primarily through multiple sp1 binding sites in the proximal promoter. Oncogene 25, 3296–3306 (2006). https://doi.org/10.1038/sj.onc.1209363

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