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 04:00:00 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), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 89:3; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

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