Serum response factor has functional roles both in indirect binding to the CArG box and in the transcriptional activation function of human T-cell leukemia virus type I Tax.
We previously reported that Tax1 of human T-cell leukemia virus type I interacts directly with serum response factor (SRF) and that Tax1 activates the transcription of several cellular immediate-early genes through the SRF binding site (CArG box). This activation required the transcriptional activation function of Tax1, identified as an activity of GALTax (a chimeric Tax1 with the yeast transcription factor GAL4) at the GAL4-binding site. In this study, we examined whether SRF plays a role in the transcriptional activation function of Tax1. Expression of Tax1 suppressed the GALTax activity at the GAL4 site as a result of squelching, and the suppressed activity was recovered by the overexpression of SRF, suggesting that SRF is a factor that is required for GALTax activity and that is inhibited by competition with Tax1. The expression of antisense SRF RNA specifically inhibited GALTax activity to less than 20%. Deletion of the Tax1 interaction domain of SRF at its C terminus converted SRF from an activator of GALTax to an inhibitor. These results suggest that SRF is an essential component of the transcriptional activation of Tax1 in addition to a mediator of CArG box binding.
Fujii
M
M
Department of Molecular Virology and Oncology, Kanazawa University, Ishikawa, Japan.
Tsuchiya
H
H
Chuhjo
T
T
Minamino
T
T
Miyamoto
K
K
Seiki
M
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005656:Fungal Proteins / Q000502:physiology; D016356:Gene Products, tax / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D026362:Serum Response Factor; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D016356:Gene Products, tax; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D026362:Serum Response Factor; D014157:Transcription Factors