Hyun-Jung An" /> Hyun-Jung An, Hayyoung Lee*, and Sang-Gi Paik*

" /> Hyun-Jung An, Hayyoung Lee*, and Sang-Gi Paik*

. Mol. Cells 2011;31:579-83. https://doi.org/10.1007/s10059-011-0065-z">
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Mol. Cells 2011; 31(6): 579-583

Published online May 11, 2011

https://doi.org/10.1007/s10059-011-0065-z

© The Korean Society for Molecular and Cellular Biology

Silencing of BNIP3 Results from Promoter Methylation by DNA Methyltransferase 1 Induced by the Mitogen-Activated Protein Kinase Pathway

Hyun-Jung An1,2, Hayyoung Lee3,*, and Sang-Gi Paik1,2,*

1Department of Biology, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Korea, 2Brain Korea 21 Daedeok R&D Innopolis Bio Brain Center, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Korea, 3Institute of Biotechnology, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Korea

Correspondence to : *Correspondence: hlee@cnu.ac.kr (HL); sgpaik@cnu.ac.kr (SGP)

Received: April 4, 2011; Accepted: April 18, 2011

Abstract

We have previously shown that Ras mediates NO-induced BNIP3 expression via the MEK-ERK-HIF-1 pathway in mouse macrophages, and that NO-induced death results at least in part from the induction of BNIP3. In the present study, we describe another aspect of Ras regulation of BNIP3 expression in pancreatic cancer cells. Human BNIP3 promoter-driven luciferase activity was efficiently induced by activated Ras in AsPC-1, Miapaca-2, PK-1 and PANC-1 cells. However, expression of endoge-nous BNIP3 was not induced, and BNIP3 up-regulation by hypoxia was also inhibited. Treatment of the cells with the DNMT inhibitor, 5-aza-2-deoxycytidine, restored BNIP3 induction, indicating that DNA methylation of the BNIP3 promoter was respon-sible for the inhibition of BNIP3 induction. Furthermore, inhibition of the MEK pathway with U0126 reduced DNMT1 expression, but not that of DNMT3a and 3b, and restored the hypoxia-inducibility of BNIP3, suggesting that the DNA methylation of the BNIP3 promoter was mediated by DNMT1 via the MEK pathway.

Keywords BNIP3, DNMT1, MEK, methylation, Ras

Article

Research Article

Mol. Cells 2011; 31(6): 579-583

Published online June 30, 2011 https://doi.org/10.1007/s10059-011-0065-z

Copyright © The Korean Society for Molecular and Cellular Biology.

Silencing of BNIP3 Results from Promoter Methylation by DNA Methyltransferase 1 Induced by the Mitogen-Activated Protein Kinase Pathway

Hyun-Jung An1,2, Hayyoung Lee3,*, and Sang-Gi Paik1,2,*

1Department of Biology, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Korea, 2Brain Korea 21 Daedeok R&D Innopolis Bio Brain Center, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Korea, 3Institute of Biotechnology, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Korea

Correspondence to:*Correspondence: hlee@cnu.ac.kr (HL); sgpaik@cnu.ac.kr (SGP)

Received: April 4, 2011; Accepted: April 18, 2011

Abstract

We have previously shown that Ras mediates NO-induced BNIP3 expression via the MEK-ERK-HIF-1 pathway in mouse macrophages, and that NO-induced death results at least in part from the induction of BNIP3. In the present study, we describe another aspect of Ras regulation of BNIP3 expression in pancreatic cancer cells. Human BNIP3 promoter-driven luciferase activity was efficiently induced by activated Ras in AsPC-1, Miapaca-2, PK-1 and PANC-1 cells. However, expression of endoge-nous BNIP3 was not induced, and BNIP3 up-regulation by hypoxia was also inhibited. Treatment of the cells with the DNMT inhibitor, 5-aza-2-deoxycytidine, restored BNIP3 induction, indicating that DNA methylation of the BNIP3 promoter was respon-sible for the inhibition of BNIP3 induction. Furthermore, inhibition of the MEK pathway with U0126 reduced DNMT1 expression, but not that of DNMT3a and 3b, and restored the hypoxia-inducibility of BNIP3, suggesting that the DNA methylation of the BNIP3 promoter was mediated by DNMT1 via the MEK pathway.

Keywords: BNIP3, DNMT1, MEK, methylation, Ras

Mol. Cells
May 31, 2023 Vol.46 No.5, pp. 259~328
COVER PICTURE
The alpha-helices in the lamin filaments are depicted as coils, with different subdomains distinguished by various colors. Coil 1a is represented by magenta, coil 1b by yellow, L2 by green, coil 2a by white, coil 2b by brown, stutter by cyan, coil 2c by dark blue, and the lamin Ig-like domain by grey. In the background, cells are displayed, with the cytosol depicted in green and the nucleus in blue (Ahn et al., pp. 309-318).

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