Constitutive expression of the HTLV-I pX and env regions in Jurkat T-cells induces differential activation of SRE, CRE and NF kappa B pathways.
Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia/lymphoma (ATLL). HTLV Tax, the viral transcriptional activator, can activate a variety of cellular genes. HTLV-mediated T-cell transformation, however, may involve additional viral proteins expressed from singly- as well as doubly-spliced viral mRNA. To determine the combined effect of these viral proteins on cellular gene expression in Jurkat T-cells, we derived stable transfectants that constitutively express the HTLV-I pX and env regions (J3.9). J3.9 cells show substantially increased mRNA levels of egr-1 and c-jun but no induction of either CD25 or GM-CSF by Northern blotting. This pattern corresponded to the activation of an egr-1 but not a GM-CSF promoter-driven reporter construct in transient gene expression assays. In DNA electrophoretic mobility shift assays (EMSA), nuclear extract from J3.9 cells has significantly increased binding to CRE and SRE but not nuclear factor kappa B (NF kappa B) DNA oligos, as compared to J-Neo cell extract. These results suggest that low level expression of pX and env region gene products in Jurkat T-cells stimulates persistent activation of CRE- and SRE- but not NF kappa B-induced cellular genes.
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Department of Medicine, UCLA School of Medicine 90095-1678, USA.
Luo
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Chun
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Tabibzadeh
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D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D015967:Gene Expression Regulation, Viral; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D026362:Serum Response Factor; D014157:Transcription Factors / Q000235:genetics; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D015682:Retroviridae Proteins, Oncogenic; D026362:Serum Response Factor; D014157:Transcription Factors; D014759:Viral Envelope Proteins; D054334:Viral Regulatory and Accessory Proteins; C072343:pX protein, Human T-lymphotropic virus 1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor