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http://dx.doi.org/10.14348/molcells.2015.0086

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)
Publication Information
Molecules and Cells / v.38, no.8, 2015 , pp. 705-714 More about this Journal
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.
Keywords
anti-cancer drug-resistance; expression regulation; HDAC3; tubulin beta 3;
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