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M9640711.TXT
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1996-03-04
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Document 0711
DOCN M9640711
TI Modulation of Tax and PKA-mediated expression of HTLV-I promoter via
cAMP response element binding and modulator proteins CREB and CREM.
DT 9604
AU Bodor J; Walker W; Flemington E; Spetz AL; Habener JF; Laboratory of
Molecular Endocrinology, Massachusetts General; Hospital (WEL320),
Howard Hughes Medical Institute, Boston 02114,; USA.
SO FEBS Lett. 1995 Dec 27;377(3):413-8. Unique Identifier : AIDSLINE
MED/96140558
AB Nuclear proteins of the human peripheral blood T lymphocytes that bind
to the CREs located within three 21-bp repeat enhancers of the HTLV-I
promoter belong to the CREB/CREM family of bZIP transcription factors.
It has been shown previously that Tax enhances transactivation of these
CREs by direct interactions with the bZIP domain of the transcription
factors to stabilize DNA-binding. We show that CREB and CREM bind all
three CRE sequences of the HTLV-I promoter which are important
determinants in Tax-elicited transactivation as well as PKA-mediated
activation of the HTLV-I promoter. Tax and PKA activate transcription
from a HTLV-I-LTR CAT reporter plasmid transfected to NIH 3T3 cells, and
CREM attenuates the activation. In the context of a GAL4 CREB fusion
protein in which the DNA-binding bZIP domain of CREB is replaced by GAL4
binding domain, a single amino acid substitution of serine-133,
phosphorylated by PKA and critical for the transactivation function of
CREB, attenuates both Tax and PKA-mediated transcriptional responses.
These observations suggest that Tax enhances CREB-mediated
transactivation of the HTLV-I promoter by a mechanism apart from, and/or
in addition to, the reported stabilization of DNA-binding by interaction
with the bZIP domain of CREB.
DE Animal Base Sequence Binding Sites Cyclic AMP-Dependent Protein
Kinases/METABOLISM DNA-Binding Protein, Cyclic
AMP-Responsive/METABOLISM DNA-Binding Proteins/METABOLISM Human
HTLV-I/*GENETICS Mice Molecular Sequence Data Nuclear
Proteins/METABOLISM *Promoter Regions (Genetics) Protein Binding
Proteins/METABOLISM *Repetitive Sequences, Nucleic Acid Support,
Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes/METABOLISM
*Trans-Activation (Genetics) *Transcription, Genetic Transfection 3T3
Cells JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).