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Modulation of tax and PKA‐mediated expression of HTLV‐I promoter via cAMP response element binding and modulator proteins CREB and CREM
Author(s) -
Josef Bodor,
William H. Walker,
Erik K. Flemington,
Anita Lloyd-Spetz,
Joel F. Habener
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01299-0
Subject(s) - creb , transactivation , bzip domain , transcription factor , activating transcription factor , creb binding protein , dna binding domain , enhancer , transcription (linguistics) , promoter , microbiology and biotechnology , response element , creb1 , biology , chemistry , genetics , gene expression , gene , linguistics , philosophy
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.