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 D 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

doi:10.1371/journal.pone.0051407

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 D 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

Research output: Contribution to journal › Article › peer-review

76 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 language	English (US)
Article number	e51407
Journal	PLoS One
Volume	7
Issue number	12
DOIs	https://doi.org/10.1371/journal.pone.0051407
State	Published - Dec 7 2012
Externally published	Yes

ASJC Scopus subject areas

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

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10.1371/journal.pone.0051407

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Ene, C. I., Edwards, L., Riddick, G., Baysan, M., Woolard, K. D., 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

Histone Demethylase Jumonji D3 (JMJD3) as a Tumor Suppressor by Regulating p53 Protein Nuclear Stabilization. / Ene, Chibawanye I.; Edwards, Lincoln; Riddick, Gregory; Baysan, Mehmet; Woolard, Kevin D; Kotliarova, Svetlana; Lai, Chen; Belova, Galina; Cam, Maggie; Walling, Jennifer; Zhou, Ming; Stevenson, Holly; Kim, Hong Sug; Killian, Keith; Veenstra, Timothy; Bailey, Rolanda; Song, Hua; Zhang, Wei; Fine, Howard A.

In: PLoS One, Vol. 7, No. 12, e51407, 07.12.2012.

Research output: Contribution to journal › Article › peer-review

Ene, CI, Edwards, L, Riddick, G, Baysan, M, Woolard, KD, Kotliarova, S, Lai, C, Belova, G, Cam, M, Walling, J, Zhou, M, Stevenson, H, Kim, HS, Killian, K, Veenstra, T, Bailey, R, Song, H, Zhang, W & Fine, HA 2012, 'Histone Demethylase Jumonji D3 (JMJD3) as a Tumor Suppressor by Regulating p53 Protein Nuclear Stabilization', PLoS One, vol. 7, no. 12, e51407. https://doi.org/10.1371/journal.pone.0051407

Ene, Chibawanye I. ; Edwards, Lincoln ; Riddick, Gregory ; Baysan, Mehmet ; Woolard, Kevin D ; Kotliarova, Svetlana ; Lai, Chen ; Belova, Galina ; Cam, Maggie ; Walling, Jennifer ; Zhou, Ming ; Stevenson, Holly ; Kim, Hong Sug ; Killian, Keith ; Veenstra, Timothy ; Bailey, Rolanda ; Song, Hua ; Zhang, Wei ; Fine, Howard A. / Histone Demethylase Jumonji D3 (JMJD3) as a Tumor Suppressor by Regulating p53 Protein Nuclear Stabilization. In: PLoS One. 2012 ; Vol. 7, No. 12.

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AU - Killian, Keith

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AU - Fine, Howard A.

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

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