HTLV-1 oncoprotein Tax deregulates transcription of cellular genes through multiple mechanisms.
Infection of a human retrovirus HTLV-1 induces adult T cell leukemia and a neurological disease, HAM/TSP. Regulatory protein Tax of HTLV-1 is thought to contribute to the pathogenesis. We have studied the mechanism of transcriptional activation induced by Tax protein and identified two independent mechanisms: (a) binding to the enhancer-binding proteins, CREB, CREM, NF-kappa B and SRF, resulting in the activation of these factors through indirect binding to each specific DNA sequence, and (b) binding to I kappa B protein resulting in the suppression of the negative regulator I kappa B, which binds to NF-kappa B. In addition to these factors, a new protein GLI/THP is also involved in the transactivation. On the basis of these mechanisms, gene regulations in vitro and in vivo in HTLV-1-infected cells are discussed.
Yoshida
M
M
Department of Cellular and Molecular Biology, University of Tokyo, Japan.
D001483:Base Sequence; D002472:Cell Transformation, Viral; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D026362:Serum Response Factor; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000075746:Zinc Finger Protein Gli2
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C082593:GLI2 protein, human; D016356:Gene Products, tax; D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; C497593:RELB protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D000075746:Zinc Finger Protein Gli2; D051786:Cyclic AMP Response Element Modulator; D051841:Transcription Factor RelB