Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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8-60hIPP5m-Induced G2/M Cell Cycle Arrest Involves Activation of ATM/p53/p21cip1/waf1 Pathways and Delayed Cyclin B1 Nuclear Translocation

  • Zeng, Qi-Yan (Department of Biochemistry and Molecular Biology, Guangxi Medical University) ;
  • Zeng, Lin-Jie (Department of Orthopaedics, Orthopaedics Hospital) ;
  • Huang, Yu (Clinical Laboratory Center, Nanfang Hospital) ;
  • Huang, Yong-Qi (Department of Biochemistry and Molecular Biology, Guangxi Medical University) ;
  • Zhu, Qi-Fang (Department of Biochemistry and Molecular Biology, Guangxi Medical University) ;
  • Liao, Zhi-Hong (Department of Biochemistry and Molecular Biology, Guangxi Medical University)
  • Published : 2014.05.15
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Abstract

Protein phosphatase 1 (PP1) is a major serine/threonine phosphatase that controls gene expression and cell cycle progression. The active mutant IPP5 ($8-60hIPP5^m$), the latest member of the inhibitory molecules for PP1, has been shown to inhibit the growth of human cervix carcinoma cells (HeLa). In order to elucidate the underlying mechanisms, the present study assessed overexpression of $8-60hIPP5^m$ in HeLa cells. Flow cytometric and biochemical analyses showed that overexpression of $8-60hIPP5^m$ induced G2/M-phase arrest, which was accompanied by the upregulation of cyclin B1 and phosphorylation of G2/M-phase proteins ATM, p53, $p21^{cip1/waf1}$ and Cdc2, suggesting that $8-60hIPP5^m$ induces G2/M arrest through activation of the ATM/p53/$p21^{cip1/waf1}$/Cdc2/cyclin B1 pathways. We further showed that overexpression of $8-60hIPP5^m$ led to delayed nuclear translocation of cyclin B1. $8-60hIPP5^m$ also could translocate to the nucleus in G2/M phase and interact with $pp1{\alpha}$ and Cdc2 as demonstrated by co-precipitation assay. Taken together, our data demonstrate a novel role for $8-60hIPP5^m$ in regulation of cell cycle in HeLa cells, possibly contributing to the development of new therapeutic strategies for cervix carcinoma.

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References

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