Histone Demethylase Jumonji D3 (JMJD3) as a Tumor Suppressor by Regulating p53 Protein Nuclear Stabilization

Chibawanye I. Ene, Lincoln Edwards, Gregory Riddick, Mehmet Baysan, Kevin Woolard, Svetlana Kotliarova, Chen Lai, Galina Belova, Maggie Cam, Jennifer Walling, Ming Zhou, Holly Stevenson, Hong Sug Kim, Keith Killian, Timothy Veenstra, Rolanda Bailey, Hua Song, Wei Zhang, Howard A. Fine

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68 Scopus citations

Abstract

Histone methylation regulates normal stem cell fate decisions through a coordinated interplay between histone methyltransferases and demethylases at lineage specific genes. Malignant transformation is associated with aberrant accumulation of repressive histone modifications, such as polycomb mediated histone 3 lysine 27 (H3K27me3) resulting in a histone methylation mediated block to differentiation. The relevance, however, of histone demethylases in cancer remains less clear. We report that JMJD3, a H3K27me3 demethylase, is induced during differentiation of glioblastoma stem cells (GSCs), where it promotes a differentiation-like phenotype via chromatin dependent (INK4A/ARF locus activation) and chromatin independent (nuclear p53 protein stabilization) mechanisms. Our findings indicate that deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation.

Original languageEnglish (US)
Article numbere51407
JournalPLoS One
Volume7
Issue number12
DOIs
StatePublished - Dec 7 2012

ASJC Scopus subject areas

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

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    Ene, C. I., Edwards, L., Riddick, G., Baysan, M., Woolard, K., Kotliarova, S., Lai, C., Belova, G., Cam, M., Walling, J., Zhou, M., Stevenson, H., Kim, H. S., Killian, K., Veenstra, T., Bailey, R., Song, H., Zhang, W., & Fine, H. A. (2012). Histone Demethylase Jumonji D3 (JMJD3) as a Tumor Suppressor by Regulating p53 Protein Nuclear Stabilization. PLoS One, 7(12), [e51407]. https://doi.org/10.1371/journal.pone.0051407