title: Requirement of a novel splicing variant of human histone deacetylase 6 for TGF-beta1-mediated gene activation.
abstract: Histone deacetylase 6 (HDAC6) belongs to the family of class IIb HDACs and predominantly deacetylates non-histone proteins in the cytoplasm via the C-terminal deacetylase domain of its two tandem deacetylase domains. HDAC6 modulates fundamental cellular processes via deacetylation of alpha-tubulin, cortactin, molecular chaperones, and other peptides. Our previous study indicates that HDAC6 mediates TGF-beta1-induced epithelial-mesenchymal transition (EMT) in A549 cells. In the current study, we identify a novel splicing variant of human HDAC6, hHDAC6p114. The hHDAC6p114 mRNA arises from incomplete splicing and encodes a truncated isoform of the hHDAC6p114 protein of 114kDa when compared to the major isoform hHDAC6p131. The hHDAC6p114 protein lacks the first 152 amino acids from N-terminus in the hHDAC6p131 protein, which harbors a nuclear export signal peptide and 76 amino acids of the N-terminal deacetylase domain. hHDAC6p114 is intact in its deacetylase activity against alpha-tubulin. The expression hHDAC6p114 is elevated in a MCF-7 derivative that exhibits an EMT-like phenotype. Moreover, hHDAC6p114 is required for TGF-beta1-activated gene expression associated with EMT in A549 cells. Taken together, our results implicate that expression and function of hHDAC6p114 is differentially regulated when compared to hHDAC6p131.
authors.affiliation: Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Hong T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lasky
authors.forename: Subing
authors.initials: S
authors.lastname: Cao
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.forename: Jiyao
authors.initials: J
authors.lastname: Hu
authors.forename: Xinyue
authors.initials: X
authors.lastname: Guo
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Burow
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D053773:Transforming Growth Factor beta1; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases