Identification of poly(ADP-ribose) polymerase-1 as a cell cycle regulator through modulating Sp1 mediated transcription in human hepatoma cells

Liu Yang, Kun Huang, Xiangrao Li, Meng Du, Xiang Kang, Xi Luo, Lu Gao, Cheng Wang, Yanqing Zhang, Chun Zhang, Qiangsong Tong, Kai Huang, Fengxiao Zhang, Dan Huang

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The transcription factor Sp1 is implicated in the activation of G0/G1 phase genes. Modulation of Sp1 transcription activities may affect G1-S checkpoint, resulting in changes in cell proliferation. In this study, our results demonstrated that activated poly(ADP-ribose) polymerase 1 (PARP-1) promoted cell proliferation by inhibiting Sp1 signaling pathway. Cell proliferation and cell cycle assays demonstrated that PARP inhibitors or PARP-1 siRNA treatment significantly inhibited proliferation of hepatoma cells and induced G0/G1 cell cycle arrest in hepatoma cells, while overexpression of PARP-1 or PARP-1 activator treatment promoted cell cycle progression. Simultaneously, inhibition of PARP-1 enhanced the expression of Sp1-mediated checkpoint proteins, such as p21 and p27. In this study, we also showed that Sp1 was poly(ADP-ribosyl)ated by PARP-1 in hepatoma cells. Poly(ADP-ribosyl)ation suppressed Sp1 mediated transcription through preventing Sp1 binding to the Sp1 response element present in the promoters of target genes. Taken together, these data indicated that PARP-1 inhibition attenuated the poly(ADP-ribosyl)ation of Sp1 and significantly increased the expression of Sp1 target genes, resulting in G0/G1 cell cycle arrest and the decreased proliferative ability of the hepatoma cells.

Original languageEnglish (US)
Article numbere82872
JournalPloS one
Volume8
Issue number12
DOIs
StatePublished - Dec 19 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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  • Cite this

    Yang, L., Huang, K., Li, X., Du, M., Kang, X., Luo, X., Gao, L., Wang, C., Zhang, Y., Zhang, C., Tong, Q., Huang, K., Zhang, F., & Huang, D. (2013). Identification of poly(ADP-ribose) polymerase-1 as a cell cycle regulator through modulating Sp1 mediated transcription in human hepatoma cells. PloS one, 8(12), [e82872]. https://doi.org/10.1371/journal.pone.0082872