Jmjd2c histone demethylase enhances the expression of Mdm2 oncogene

Akihiko Ishimura; Minoru Terashima; Hiroshi Kimura; Keiko Akagi; Yutaka Suzuki; Sumio Sugano; Takeshi Suzuki

doi:10.1016/j.bbrc.2009.08.155

Jmjd2c histone demethylase enhances the expression of Mdm2 oncogene

Akihiko Ishimura, Minoru Terashima, Hiroshi Kimura, Keiko Akagi, Yutaka Suzuki, Sumio Sugano, Takeshi Suzuki

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

50 Scopus citations

Abstract

Jmjd2c is a candidate oncogene that encodes histone lysine demethylase. In this study, we discovered that over-expression of Jmjd2c increased the expression of Mdm2 oncogene dependent on its demethylase activity, which led to the reduction of p53 tumor suppressor gene product in the cells. A chromatin immunoprecipitation assay showed that Jmjd2c was recruited to the P2 promoter region of Mdm2 gene resulting in demethylation of histone H3 lysine 9, as typically found in actively transcribed genes. Furthermore, siRNA-mediated knockdown of Jmjd2c caused the reduction of Mdm2 expression in the cells. These results indicate that Mdm2 oncogene is a downstream target of Jmjd2c and may play an important role in Jmjd2c-mediated oncogenesis.

Original language	English (US)
Pages (from-to)	366-371
Number of pages	6
Journal	Biochemical and biophysical research communications
Volume	389
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2009.08.155
State	Published - Nov 13 2009
Externally published	Yes

Keywords

Histone demethylase
JmjC-domain
Oncogene
Transcription
p53

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2009.08.155

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title = "Jmjd2c histone demethylase enhances the expression of Mdm2 oncogene",

abstract = "Jmjd2c is a candidate oncogene that encodes histone lysine demethylase. In this study, we discovered that over-expression of Jmjd2c increased the expression of Mdm2 oncogene dependent on its demethylase activity, which led to the reduction of p53 tumor suppressor gene product in the cells. A chromatin immunoprecipitation assay showed that Jmjd2c was recruited to the P2 promoter region of Mdm2 gene resulting in demethylation of histone H3 lysine 9, as typically found in actively transcribed genes. Furthermore, siRNA-mediated knockdown of Jmjd2c caused the reduction of Mdm2 expression in the cells. These results indicate that Mdm2 oncogene is a downstream target of Jmjd2c and may play an important role in Jmjd2c-mediated oncogenesis.",

keywords = "Histone demethylase, JmjC-domain, Oncogene, Transcription, p53",

author = "Akihiko Ishimura and Minoru Terashima and Hiroshi Kimura and Keiko Akagi and Yutaka Suzuki and Sumio Sugano and Takeshi Suzuki",

note = "Funding Information: We thank Dr. T. Nakamura and Dr. T. Kitamura for providing the expression vector and the packaging cell line, respectively. We thank Dr. M. Yoshida for helpful discussion and Dr. M. Takahashi for critical reading of the manuscript. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Research Grant from Inamori Foundation .",

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doi = "10.1016/j.bbrc.2009.08.155",

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AU - Ishimura, Akihiko

AU - Terashima, Minoru

AU - Kimura, Hiroshi

AU - Akagi, Keiko

AU - Suzuki, Yutaka

AU - Sugano, Sumio

AU - Suzuki, Takeshi

N1 - Funding Information: We thank Dr. T. Nakamura and Dr. T. Kitamura for providing the expression vector and the packaging cell line, respectively. We thank Dr. M. Yoshida for helpful discussion and Dr. M. Takahashi for critical reading of the manuscript. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Research Grant from Inamori Foundation .

PY - 2009/11/13

Y1 - 2009/11/13

N2 - Jmjd2c is a candidate oncogene that encodes histone lysine demethylase. In this study, we discovered that over-expression of Jmjd2c increased the expression of Mdm2 oncogene dependent on its demethylase activity, which led to the reduction of p53 tumor suppressor gene product in the cells. A chromatin immunoprecipitation assay showed that Jmjd2c was recruited to the P2 promoter region of Mdm2 gene resulting in demethylation of histone H3 lysine 9, as typically found in actively transcribed genes. Furthermore, siRNA-mediated knockdown of Jmjd2c caused the reduction of Mdm2 expression in the cells. These results indicate that Mdm2 oncogene is a downstream target of Jmjd2c and may play an important role in Jmjd2c-mediated oncogenesis.

AB - Jmjd2c is a candidate oncogene that encodes histone lysine demethylase. In this study, we discovered that over-expression of Jmjd2c increased the expression of Mdm2 oncogene dependent on its demethylase activity, which led to the reduction of p53 tumor suppressor gene product in the cells. A chromatin immunoprecipitation assay showed that Jmjd2c was recruited to the P2 promoter region of Mdm2 gene resulting in demethylation of histone H3 lysine 9, as typically found in actively transcribed genes. Furthermore, siRNA-mediated knockdown of Jmjd2c caused the reduction of Mdm2 expression in the cells. These results indicate that Mdm2 oncogene is a downstream target of Jmjd2c and may play an important role in Jmjd2c-mediated oncogenesis.

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KW - Transcription

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Jmjd2c histone demethylase enhances the expression of Mdm2 oncogene

Abstract

Keywords

ASJC Scopus subject areas

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