Molecular cloning and characterization of a novel histone deacetylase HDAC10.
The growing number of proteins controlled by reversible acetylation suggests the existence of a large number of acetyltransferases and deacetylases. Here, we report the identification of a novel class II histone deacetylase, HDAC10. Homology comparison indicates that HDAC10 is most similar to HDAC6. Both contain a unique, putative second catalytic domain not found in other HDACs. In HDAC10, however, this domain is not functional. This tandem organization of two catalytic domains confers resistance to the inhibitors trapoxin B and sodium butyrate, which potently inhibit the deacetylase activity of all other HDAC members. Thus, HDAC10 and HDAC6 share unusual structural and pharmacological characteristics. However, unlike HDAC6, which is normally a cytoplasmic deacetylase, HDAC10 resides in both the nucleus and cytoplasm. In the nucleus, when tethered to a promoter, HDAC10 represses transcription independent of its deacetylase activity, indicating that HDAC10 contains a distinct transcriptional repressor domain. These observations suggest that HDAC10 might uniquely play roles both in the nucleus, as a transcriptional modulator, and in the cytoplasm in an unidentified role. Together, our results identify HDAC10 as a novel deacetylase with distinct structure, pharmacology and localization and further expand the complexity of the HDAC family.
Guardiola
Amaris R
AR
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Yao
Tso-Pang
TP
D000595:Amino Acid Sequence; D020134:Catalytic Domain; D002460:Cell Line; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D017931:DNA Primers; D005786:Gene Expression Regulation; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection
D017931:DNA Primers; D011994:Recombinant Proteins; D012097:Repressor Proteins; C447828:HDAC10 protein, human; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases