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Transcription factor Sp1 prevents TRF2ΔBΔM-induced premature senescence in human diploid fibroblasts

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Abstract

Telomere uncap** is thought to be the fundamental cause of replicative cellular senescence, but the cellular machineries mediating this process have not been fully understood. In the present study, we present the role of Sp1 transcription factor in the state of telomere uncap** using the TRF2ΔBΔM-induced senescence model in human diploid fibroblasts. We observed that the expression of Sp1 is down-regulated in the TRF2ΔBΔM-induced senescence, which was mediated by ATM and p38 MAPK. In addition, overexpression of Sp1 prevented the TRF2ΔBΔM-induced senescence. Among transcriptional targets of Sp1, expression levels of nuclear transport genes such as karyopherin α, Nup107, and Nup50 were down-regulated in the TRF2ΔBΔM-induced senescence, which was prevented by Sp1 overexpression. Moreover, inhibition of the nuclear transport by wheat germ agglutinin (an import inhibitor) and leptomycin B (an export inhibitor) induced premature senescence. These results suggest that Sp1 is an anti-senescence transcription factor in the telomere uncap**-induced senescence and that down-regulation of Sp1 leads to the senescence via down-regulation of the nuclear transport.

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Abbreviations

ATM:

Ataxia telangiectasia mutated

HDF:

Human diploid fibroblast

MAPK:

Mitogen-activated protein kinase

Sp1:

Specificity protein 1

TRF2:

Telomeric repeat-binding factor 2

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Acknowledgments

This research was supported by the Basic Science Research Program through the NRF funded by the Ministry of Education, Science and Technology (2010-0007188) and by the 2015 Research Grant from Kangwon National University (No. 520150358).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea

    Hyun Ju An, Hyeon Ju Lee & Jeong A. Han

  2. Department of Biomedical Science, Graduate School of Biomedical Science & Engineering, Hanyang University, Seoul, 133-791, South Korea

    Suhwa Jang

  3. Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, 200-701, South Korea

    Yu-** Jung

  4. Department of Medical Biotechnology, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, 200-701, South Korea

    Sun Shim Choi

  5. Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 406-840, South Korea

    Sang Chul Park

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  1. Hyun Ju An
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Correspondence to Jeong A. Han.

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An, H.J., Lee, H.J., Jang, S. et al. Transcription factor Sp1 prevents TRF2ΔBΔM-induced premature senescence in human diploid fibroblasts. Mol Cell Biochem 414, 201–208 (2016). https://doi.org/10.1007/s11010-016-2672-7

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