The interaction of HTLV-1 Tax with HDAC1 negatively regulates the viral gene expression.
Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are known to interact with several transcription factors and regulate their transcriptional activities. The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein activates transcription from its long terminal repeat (LTR) through interaction with cellular factors such as CREB and a transcriptional coactivator CBP/p300. However, little is known about the interaction between Tax and transcriptional repressors. Here, we demonstrate the physical and functional interaction between Tax and HDAC1. We found that HDAC1 represses the trans-activation function of Tax in 293T and MT4 cells. However, this repression was restored by treatment with an HDAC inhibitor, Trichostatin A. We also observed physical interaction between Tax and HDAC1 both in vitro and in vivo. The N-terminal region of HDAC1 (amino acid residues 28-97) was required for this binding. Moreover, HDAC1 inhibited the synergistic trans-activation of Tax observed on ectopic expression of CBP. However, this repression was relieved by overexpression of CBP. Thus, HDAC1 is likely to compete with CBP in binding with Tax and functions as a negative regulator for the transcriptional activation by Tax.
Ego
Takeshi
T
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Ariumi
Yasuo
Y
Shimotohno
Kunitada
K
D000595:Amino Acid Sequence; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics* / Q000378:metabolism; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation
D016356:Gene Products, tax; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D015534:Trans-Activators; C012589:trichostatin A; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases