The FK506-binding protein 25 functionally associates with histone deacetylases and with transcription factor YY1.
FK506-binding proteins (FKBPs) are cellular receptors for immunosuppressants that belong to a subgroup of proteins, known as immunophilins, with peptidylprolyl cis-trans isomerase (PPIase) activity. Sequence comparison suggested that the HD2-type histone deacetylases and the FKBP-type PPIases may have evolved from a common ancestor enzyme. Here we show that FKBP25 physically associates with the histone deacetylases HDAC1 and HDAC2 and with the HDAC-binding transcriptional regulator YY1. An FKBP25 immunoprecipitated complex contains deacetylase activity, and this activity is associated with the N-terminus of FKBP25, distinct from the FK506/rapamycin-binding domain. Furthermore, FKBP25 can alter the DNA-binding activity of YY1. Together, our data firmly establish a relationship between histone deacetylases and the FKBP enzymes and provide a novel and critical function for the FKBPs.
Yang
W M
WM
H.Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA.
Yao
Y L
YL
Seto
E
E
D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D004926:Escherichia coli; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008156:Luciferases / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C074856:FKBP3 protein, human; D008156:Luciferases; D005982:Glutathione Transferase; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D022021:Tacrolimus Binding Proteins