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KMID : 0624620140470060342
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BMB Reports
2014 Volume.47 No. 6 p.342 ~ p.347
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Nuclear localization signal domain of HDAC3 is necessary and sufficient for the expression regulation of MDR1
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Park Hyun-Mi
Kim Young-Mi
Park Deok-Bum
Jeoung Doo-Il
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Abstract
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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 HDAC3S424A, negatively regulated the expression of MDR1. Wild-type HDAC3, but not catalytic mutant HDAC3S424A, showed binding to the promoter sequences of HDAC3. HDAC3 regulated the expression level, and the binding of Ac-H3K9/14 and Ac-H4K16 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.
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KEYWORD
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Anti-cancer drug-resistance, Expression regulation, Histone deacetylase-3, MDR1, Nuclear localization
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