Laboratory of Molecular Endocrinology, Massachusetts General Hospital (WEL320), Howard Hughes Medical Institute, Boston 02114, USA.
FEBS Lett 377: 413-8 (1995)
Abstract
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.
Mesh Headings
Unique Identifier: 96140558
Chemical Identifiers (Names)