BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Nuclear localization signal domain of HDAC3 is necessary and sufficient for the expression regulation of MDR1

  • Park, Hyunmi (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Kim, Youngmi (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Park, Deokbum (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Jeoung, Dooil (Department of Biochemistry, College of Natural Sciences, Kangwon National University)
  • Received : 2013.07.25
  • Accepted : 2013.10.18
  • Published : 2014.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Histone acetylation/deacetylation has been known to be associated with the transcriptional regulation of various genes. The role of histone deacetylase-3 in the expression regulation of MDR1 was investigated. The expression level of HDAC3 showed an inverse relationship with the expression level of MDR1. Wild-type HDAC3, but not catalytic mutant $HDAC3^{S424A}$, negatively regulated the expression of MDR1. Wild-type HDAC3, but not catalytic mutant $HDAC3^{S424A}$, showed binding to the promoter sequences of HDAC3. HDAC3 regulated the expression level, and the binding of Ac-$H3^{K9/14}$ and Ac-$H4^{K16}$ around the MDR1 promoter sequences. The nuclear localization signal domain of HDAC3 was necessary, and sufficient for the binding of HDAC3 to the MDR1 promoter sequences and for conferring sensitivity to microtubule-targeting drugs.

Keywords

References

  1. Mahlknecht, U., Emiliani, S., Najfeld, V., Young, S. and E. Verdin, E. (1999) Genomic organization and chromosomal localization of the human histone deacetylase 3 gene. Genomics 56, 197-202. https://doi.org/10.1006/geno.1998.5645
  2. Li, J., Wang, J., Wang, J., Nawaz, Z., Liu, J. M., Qin, J. and Wong, J. (2000) Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3. EMBO J. 19, 4342-4350. https://doi.org/10.1093/emboj/19.16.4342
  3. Zhang, J., Kalkum, M., Chait, B. T. and Roeder, R. G. (2002) The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2. Mol. Cell 9, 611-623. https://doi.org/10.1016/S1097-2765(02)00468-9
  4. Mahlknecht, U., Will, J., Varin, A., Hoelzer, D. and Herbein, G. (2004) Histone deacetylase 3, a class I histone deacetylase, suppresses MAPK11-mediated activating transcription factor-2 activation and represses TNF gene expression. J. Immunol. 173, 3979-3990. https://doi.org/10.4049/jimmunol.173.6.3979
  5. Bardai, F. H. and D'Mello, S. R. (2011) Selective toxicity by HDAC3 in neurons: regulation by Akt and GSK3beta. J. Neurosci. 31, 1746-1751. https://doi.org/10.1523/JNEUROSCI.5704-10.2011
  6. Kim, H. C., Choi, K. C., Choi, H. K., Kang, H. B., Kim, M. J., Lee, Y. H., Lee, O. H., Lee, J., Kim, Y. J., Jun, W., Jeong, J. W. and Yoon, H. G. (2010) HDAC3 selectively represses CREB3-mediated transcription and migration of metastatic breast cancer cells. Cell. Mol. Life Sci. 67, 3499-3510. https://doi.org/10.1007/s00018-010-0388-5
  7. Ott, P. A., Chang, J., Madden, K., Kannan, R., Muren, C., Escano, C., Cheng, X., Shao, Y., Mendoza, S., Gandhi, A., Liebes, L. and Pavlick, A. C. (2013) Oblimersen in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma: a phase I trial. Cancer Chemother. Pharmacol. 71, 183-191. https://doi.org/10.1007/s00280-012-1995-7
  8. Chae, S., Kim, Y. B., Lee, J. S. and Cho, H. (2012) Resistance to paclitaxel in hepatoma cells is related to static JNK activation and prohibition into entry of mitosis. Am. J. Physiol. Gastrointest. Liver Physiol. 302, 1016-1024. https://doi.org/10.1152/ajpgi.00449.2011
  9. Xu, R., Sato, N., Yanai, K., Akiyoshi, T., Nagai, S., Wada, J., Koga, K., Mibu, R., Nakamura, M., and Katano, M. (2009) Enhancement of paclitaxel-induced apoptosis by inhibition of mitogen-activated protein kinase pathway in colon cancer cells. Anticancer Res. 29, 261-270.
  10. Mechetner, E., Kyshtoobayeva, A., Zonis, S., Kim, H., Stroup, R., Garcia, R., Parker, R. J. and Fruehauf, J. P. (1998) Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin. Cancer Res. 4, 389-398.
  11. Yatouji, S., El-Khoury, V., Trentesaux, C., Trussardi-Regnier, A., Benabid, R., Bontems, F. and Dufer, J. (2007) Differential modulation of nuclear texture, histone acetylation, and MDR1 gene expression in human drug-sensitive and -resistant OV1 cell lines. Int. J. Oncol. 30, 1003-1009.
  12. Kim, Y. K., Kim, N. H., Hwang, J. W., Song, Y. J., Park, Y. S., Seo, D. W., Lee, H. Y., Choi, W. S., Han, J. W. and Kim, S. N. (2008) Histone deacetylase inhibitor apicidin-mediated drug resistance: involvement of P-glycoprotein. Biochem. Biophys. Res. Commun. 368, 959-964. https://doi.org/10.1016/j.bbrc.2008.02.013
  13. To, K. K., Polgar, O., Huff, L. M., Morisaki, K. and Bates, S. E. (2008) Histone modifications at the ABCG2 promoter following treatment with histone deacetylase inhibitor mirror those in multidrug-resistant cells. Mol. Cancer Res. 6, 151-164. https://doi.org/10.1158/1541-7786.MCR-07-0175
  14. Bhaskara, S., Knutson, S. K., Jiang, G., Chandrasekharan, M. B., Wilson, A. J., Zheng, S., Yenamandra, A., Locke, K., Yuan, J. L., Bonine-Summers, A. R., Wells, C. E., Kaiser, J. F., Washington, M. K., Zhao, Z., Wagner, F. F., Sun, Z. W., Xia, F., Holson, E. B., Khabele, D. and Hiebert, S. W. (2010) Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell. 18, 436-447. https://doi.org/10.1016/j.ccr.2010.10.022
  15. Toth, M., Boros, L. M. and Balint, M. (2012) Elevated level of lysine 9-acetylated histone H3 at the MDR1 promoter in multi-drug resistant cells. Cancer Science 103, 659-669. https://doi.org/10.1111/j.1349-7006.2012.02215.x
  16. Zhang, X., Ozawa, Y., Lee, H., Wen, Y. D., Tan, T. H., Wadzinski, B. E. and Seto, E. (2005) Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4. Genes Dev. 19, 827-839. https://doi.org/10.1101/gad.1286005
  17. Kim, Y., Park, H., Park, D., Lee, Y. S., Choe, J., Hahn, J. H., Lee, H., Kim, Y. M. and Jeoung, D. (2010) Cancer/testis antigen CAGE exerts negative regulation on p53 expression through HDAC2 and confers resistance to anti-cancer drugs. J. Biol. Chem. 285, 25957-25968. https://doi.org/10.1074/jbc.M109.095950
  18. Yang, W. M., Tsai, S. C., Wen, Y. D., Fejer, G. and Seto, E. (2002) Functional domains of histone deacetylase-3. J. Biol. Chem. 277, 9447-9454. https://doi.org/10.1074/jbc.M105993200
  19. Takami, Y. and Nakayama, T. (2000) N-terminal region, C-terminal region, nuclear export signal, and deacetylation activity of histone deacetylase-3 are essential for the viability of the DT40 chicken B cell line. J. Biol. Chem. 275, 16191-16201. https://doi.org/10.1074/jbc.M908066199
  20. Zhou, C., Shen, Q., Xue, J., Ji, C. and Chen, J. (2013) Overexpression of TTRAP inhibits cell growth and induces apoptosis in osteosarcoma cells. BMB Rep. 46, 113-118 https://doi.org/10.5483/BMBRep.2013.46.2.150
  21. Back, S. S., Kim, J., Choi, D., Lee, E. S., Choi, S. Y. and Han, K. (2013) Cooperative transcriptional activation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 genes by nuclear receptors including Liver-X-Receptor. BMB Rep. 46, 322-327 https://doi.org/10.5483/BMBRep.2013.46.6.246

Cited by

  1. DDX53 Regulates Cancer Stem Cell-Like Properties by Binding to SOX-2 vol.40, pp.5, 2017, https://doi.org/10.14348/molcells.2017.0001
  2. Histone Deacetylase-3/CAGE Axis Targets EGFR Signaling and Regulates the Response to Anti-Cancer Drugs vol.39, pp.3, 2016, https://doi.org/10.14348/molcells.2016.2244
  3. miR-335 Targets SIAH2 and Confers Sensitivity to Anti-Cancer Drugs by Increasing the Expression of HDAC3 vol.38, pp.6, 2015, https://doi.org/10.14348/molcells.2015.0051
  4. The effect of histone deacetylase inhibition on the expression of P-glycoprotein in human placental trophoblast cell lines vol.49, 2017, https://doi.org/10.1016/j.placenta.2016.11.011