Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Tubulin Beta3 Serves as a Target of HDAC3 and Mediates Resistance to Microtubule-Targeting Drugs

  • Kim, Youngmi (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Kim, Hyuna (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Jeoung, Dooil (Department of Biochemistry, College of Natural Sciences, Kangwon National University)
  • Received : 2015.03.31
  • Accepted : 2015.06.03
  • Published : 2015.08.31
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Abstract

We investigated the role of HDAC3 in anti-cancer drug-resistance. The expression of HDAC3 was decreased in cancer cell lines resistant to anti-cancer drugs such as celastrol and taxol. HDAC3 conferred sensitivity to these anti-cancer drugs. HDAC3 activity was necessary for conferring sensitivity to these anti-cancer drugs. The down-regulation of HDAC3 increased the expression of MDR1 and conferred resistance to anti-cancer drugs. The expression of tubulin ${\beta}3$ was increased in drug-resistant cancer cell lines. ChIP assays showed the binding of HDAC3 to the promoter sequences of tubulin ${\beta}3$ and HDAC6. HDAC6 showed an interaction with tubulin ${\beta}3$. HDAC3 had a negative regulatory role in the expression of tubulin ${\beta}3$ and HDAC6. The down-regulation of HDAC6 decreased the expression of MDR1 and tubulin ${\beta}3$, but did not affect HDAC3 expression. The down-regulation of HDAC6 conferred sensitivity to taxol. The down-regulation of tubulin ${\beta}3$ did not affect the expression of HDAC6 or MDR1. The down-regulation of tubulin ${\beta}3$ conferred sensitivity to anti-cancer drugs. Our results showed that tubulin ${\beta}3$ serves as a downstream target of HDAC3 and mediates resistance to microtubule-targeting drugs. Thus, the HDAC3-HDAC6-Tubulin ${\beta}$ axis can be employed for the development of anti-cancer drugs.

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References

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