Requirement of a novel splicing variant of human histone deacetylase 6 for TGF-beta1-mediated gene activation.
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.
Zhuang
Yan
Y
Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112, USA.
Nguyen
Hong T
HT
Lasky
Joseph A
JA
Cao
Subing
S
Li
Cui
C
Hu
Jiyao
J
Guo
Xinyue
X
Burow
Matthew E
ME
Shan
Bin
B
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
D053773:Transforming Growth Factor beta1; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases