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Human T-cell leukemia virus type 1 tax protein activates transcription through AP-1 site by inducing DNA binding activity in T cells.
Virology. 2001 Jan 05; 279(1):38-46.V

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) Tax protein induces the expression of various family members of the transcription factor AP-1, such as c-Jun, JunD, c-Fos, and Fra-1, at the level of RNA expression in T cells. We examined the activity of Tax in transcription through AP-1-binding sites (AP-1 site) in T cells. Transient transfection studies showed that Tax activated the expression of a luciferase gene regulated by two copies of an AP-1 site in the human Jurkat T-cell line. Tax activates the expression of viral and cellular genes through two different enhancers: a cAMP-responsive (CRE)-like element and a kappaB element. Two Tax mutants differentially activated expression of these two elements. Tax703 preferentially activated the kappaB element but not the CRE-like one, whereas TaxM22 showed the reverse. In addition, Tax703 and Tax, but not TaxM22, converted cell growth of a mouse T-cell line from being interleukin (IL)-2-dependent to being IL-2-independent. Unlike the wild-type Tax, Tax703 and TaxM22 only weakly activated the AP-1 site in the T-cell line. Thus, Tax seems to activate the AP-1 site via mechanisms distinct from those of kappaB or CRE-like elements, and the activation of the AP-1 site is dispensable for IL-2-independent growth of CTLL-2. Electrophoretic mobility shift assays showed that Tax induced strong binding activity to an AP-1 site in CTLL-2, whereas Tax703 did not, indicating that the induction of binding activity to the AP-1 site is essential for the transcriptional activation by Tax. The binding complex induced by Tax in CTLL-2 contained JunD and Fra-2. Other AP-1 proteins were undetectable. Activation of transcription through the AP-1 site in Jurkat cells by JunD and/or Fra-2 was weak. c-Jun, JunB, and c-Fos activation was greater, although the level was still less than that with Tax. Thus, the induction of AP-1 mRNA by Tax may not be sufficient for a complete activation of AP-1 site by Tax. Our results suggest that Tax activates the transcription of cellular genes with AP-1 sites by inducing the DNA-binding activity of AP-1 proteins in T cells, a mechanism distinct from those of CRE-like and kappaB elements.

Authors+Show Affiliations

Department of Virology, Niigata University School of Medicine, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11145887

Citation

Iwai, K, et al. "Human T-cell Leukemia Virus Type 1 Tax Protein Activates Transcription Through AP-1 Site By Inducing DNA Binding Activity in T Cells." Virology, vol. 279, no. 1, 2001, pp. 38-46.
Iwai K, Mori N, Oie M, et al. Human T-cell leukemia virus type 1 tax protein activates transcription through AP-1 site by inducing DNA binding activity in T cells. Virology. 2001;279(1):38-46.
Iwai, K., Mori, N., Oie, M., Yamamoto, N., & Fujii, M. (2001). Human T-cell leukemia virus type 1 tax protein activates transcription through AP-1 site by inducing DNA binding activity in T cells. Virology, 279(1), 38-46.
Iwai K, et al. Human T-cell Leukemia Virus Type 1 Tax Protein Activates Transcription Through AP-1 Site By Inducing DNA Binding Activity in T Cells. Virology. 2001 Jan 5;279(1):38-46. PubMed PMID: 11145887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human T-cell leukemia virus type 1 tax protein activates transcription through AP-1 site by inducing DNA binding activity in T cells. AU - Iwai,K, AU - Mori,N, AU - Oie,M, AU - Yamamoto,N, AU - Fujii,M, PY - 2001/1/9/pubmed PY - 2001/3/7/medline PY - 2001/1/9/entrez SP - 38 EP - 46 JF - Virology JO - Virology VL - 279 IS - 1 N2 - Human T-cell leukemia virus type 1 (HTLV-1) Tax protein induces the expression of various family members of the transcription factor AP-1, such as c-Jun, JunD, c-Fos, and Fra-1, at the level of RNA expression in T cells. We examined the activity of Tax in transcription through AP-1-binding sites (AP-1 site) in T cells. Transient transfection studies showed that Tax activated the expression of a luciferase gene regulated by two copies of an AP-1 site in the human Jurkat T-cell line. Tax activates the expression of viral and cellular genes through two different enhancers: a cAMP-responsive (CRE)-like element and a kappaB element. Two Tax mutants differentially activated expression of these two elements. Tax703 preferentially activated the kappaB element but not the CRE-like one, whereas TaxM22 showed the reverse. In addition, Tax703 and Tax, but not TaxM22, converted cell growth of a mouse T-cell line from being interleukin (IL)-2-dependent to being IL-2-independent. Unlike the wild-type Tax, Tax703 and TaxM22 only weakly activated the AP-1 site in the T-cell line. Thus, Tax seems to activate the AP-1 site via mechanisms distinct from those of kappaB or CRE-like elements, and the activation of the AP-1 site is dispensable for IL-2-independent growth of CTLL-2. Electrophoretic mobility shift assays showed that Tax induced strong binding activity to an AP-1 site in CTLL-2, whereas Tax703 did not, indicating that the induction of binding activity to the AP-1 site is essential for the transcriptional activation by Tax. The binding complex induced by Tax in CTLL-2 contained JunD and Fra-2. Other AP-1 proteins were undetectable. Activation of transcription through the AP-1 site in Jurkat cells by JunD and/or Fra-2 was weak. c-Jun, JunB, and c-Fos activation was greater, although the level was still less than that with Tax. Thus, the induction of AP-1 mRNA by Tax may not be sufficient for a complete activation of AP-1 site by Tax. Our results suggest that Tax activates the transcription of cellular genes with AP-1 sites by inducing the DNA-binding activity of AP-1 proteins in T cells, a mechanism distinct from those of CRE-like and kappaB elements. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/11145887/Human_T_cell_leukemia_virus_type_1_tax_protein_activates_transcription_through_AP_1_site_by_inducing_DNA_binding_activity_in_T_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(00)90669-X DB - PRIME DP - Unbound Medicine ER -