title: HDAC3 selectively represses CREB3-mediated transcription and migration of metastatic breast cancer cells.
abstract: We identified CREB3 as a novel HDAC3-interacting protein in a yeast two-hybrid screen for HDAC3-interacting proteins. Among all class I HDACs, CREB3 specifically interacts with HDAC3, in vitro and in vivo. HDAC3 efficiently inhibited CREB3-enhanced NF-κB activation, whereas the other class I HDACs did not alter NF-κB-dependent promoter activities or the expression of NF-κB target genes. Importantly, both knock-down of CREB3 and overexpression of HDAC3 suppressed the transcriptional activation of the novel CREB3-regulated gene, CXCR4. Furthermore, CREB3 was shown to bind to the CRE element in the CXCR4 promoter and to activate the transcription of the CXCR4 gene by causing dissociation of HDAC3 and subsequently increasing histone acetylation. Importantly, both the depletion of HDAC3 and the overexpression of CREB3 substantially increased the migration of MDA-MB-231 metastatic breast cancer cells. Taken together, these findings suggest that HDAC3 selectively represses CREB3-mediated transcriptional activation and chemotactic signalling in human metastatic breast cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Brain Korea 21 Project for Medical Sciences, Severance Medical Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Han-Cheon
authors.initials: HC
authors.lastname: Kim
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Hyo-Kyoung
authors.initials: HK
authors.lastname: Choi
authors.forename: Hee-Bum
authors.initials: HB
authors.lastname: Kang
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Yoo-Hyun
authors.initials: YH
authors.lastname: Lee
authors.forename: Ok-Hee
authors.initials: OH
authors.lastname: Lee
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Woojin
authors.initials: W
authors.lastname: Jun
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D006655:Histone Deacetylases; D016328:NF-kappa B; D019718:Receptors, CXCR4; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C107941:CREB3 protein, human; C527276:CXCR4 protein, human
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