Transactivation of the proenkephalin gene promoter by the Tax sub 1 protein of human T-cell lymphotropic virus type I

Journal Article · Sat Feb 01 00:00:00 EST 1992 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.89.3.1006· OSTI ID:5560565

Joshi, J B ^[1]; Dave, H P.G. ^[2]

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1. National Heart, Lung, and Blood Inst., Bethesda, MD (United States)
2. National Inst. of Health, Bethesda, MD (United States)

Human T-cell lymphotropic virus type I (HTLV-I), an etiologic agent for adult T-cell leukemia, is strongly associated with certain neurological diseases. The HTLV-I genome encodes a protein, Tax{sub 1}, that transactivates viral gene transcription. CD4-positive T helper lymphocytes express the proenkephalin gene, and enkephalins have been implicated as neuroimmunomodulators. The authors have investigated the effect of Tax{sub 1} on the proenkephalin gene promoter in C6 rat glioma cells and demonstrated its transactivation. Analysis using 5{prime} deletion mutants of the promoter region showed that sequences upstream of base pair - 190 are necessary for maximal transactivation. Forskolin, a cAMP modulator, synergistically increased Tax{sub 1}-mediated transactivation of the proenkephalin promoter. Neither Tax{sub 1} transactivation alone nor Tax{sub 1}/cAMP synergism exclusively involved cAMP-responsive elements. Endogenous proenkephalin gene expression increased in Tax{sub 1}-expressing C6 cells. Since HTLV-I infects lymphocytes, which express proenkephalin mRNA, Tax{sub 1} transregulation of proenkephalin expression may provide bidirectional communication between the nervous and immune systems in HTLV-I-related diseases.

• OSTI ID: 5560565
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 89:3; ISSN 0027-8424
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ENKEPHALINS
GENETIC EFFECTS
GENE REPRESSORS
METABOLIC ACTIVATION
CARBON 14 COMPOUNDS
LEUKEMIA
LEUKEMIA VIRUSES
PHOSPHORUS 32
PROMOTERS
TRANSCRIPTION
VIRUSES
AUTONOMIC NERVOUS SYSTEM AGENTS
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CARBON COMPOUNDS
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ENDORPHINS
IMMUNE SYSTEM DISEASES
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LABELLED COMPOUNDS
LIGHT NUCLEI
MICROORGANISMS
NEOPLASMS
NEUROREGULATORS
NUCLEI
NUCLEOPROTEINS
ODD-ODD NUCLEI
ONCOGENIC VIRUSES
ORGANIC COMPOUNDS
PARASITES
PEPTIDES
PHOSPHORUS ISOTOPES
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550200* - Biochemistry