Differential activation of viral and cellular promoters by human T-cell lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms

Megan E. Laurance, Roland P S Kwok, Mary S. Huang, Jane P. Richards, James Lundblad, Richard Goodman

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

We have previously proposed that cAMP-responsive element-binding protein (CREB) activity is stimulated by human T-cell lymphotropic virus-1 (HTLV-1) Tax through two mechanisms that are differentially dependent upon CREB phosphorylation. We have tested this model by examining how Tax affects transcriptional activation mediated by the cAMP-responsive element (CRE) modulator (CREM). The CREM proteins are highly homologous to CREB, particularly in their DNA-binding domains and the kinase-inducible domain (KID), a region that interacts with the coactivator CREB-binding protein (CBP) in a phosphorylation-dependent manner. Despite this similarity, most CREM isoforms are transcriptional repressors. CREMα lacks the glutamine- rich domains found in CREB that are essential for transcriptional activation. We show that the normally repressive CREMα activates the HTLV-1 and cellular CREs in the presence of Tax; activation of the viral element is phosphorylation-independent, and activation of the cellular CRE is phosphorylation-dependent. CREMΔ(C-G) lacks both the KID and the glutamine- rich regions. This isoform activates the HTLV-1 long terminal repeat in a phosphorylation-independent manner, but does not activate the cellular CRE. This study suggests that Tax, interacting with the basic/zipper region of CREM, recruits CBP to the viral promoter. Tax activation of the cellular CRE depends on the KID and its ability to interact with CBP in a phosphorylation- dependent manner.

Original languageEnglish (US)
Pages (from-to)2646-2651
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number5
DOIs
StatePublished - 1997

Fingerprint

Cyclic AMP Response Element Modulator
Virus Activation
Phosphorylation
Human T-lymphotropic virus 1
T-cells
Taxation
Viruses
Modulators
Carrier Proteins
Protein Isoforms
Chemical activation
T-Lymphocytes
CREB-Binding Protein
Phosphotransferases
Glutamine
Transcriptional Activation
Terminal Repeat Sequences
Fasteners
Protein Binding
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Differential activation of viral and cellular promoters by human T-cell lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms. / Laurance, Megan E.; Kwok, Roland P S; Huang, Mary S.; Richards, Jane P.; Lundblad, James; Goodman, Richard.

In: Journal of Biological Chemistry, Vol. 272, No. 5, 1997, p. 2646-2651.

Research output: Contribution to journalArticle

@article{39ad7bf86c2545a99a16ab9ed4fe0c19,
title = "Differential activation of viral and cellular promoters by human T-cell lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms",
abstract = "We have previously proposed that cAMP-responsive element-binding protein (CREB) activity is stimulated by human T-cell lymphotropic virus-1 (HTLV-1) Tax through two mechanisms that are differentially dependent upon CREB phosphorylation. We have tested this model by examining how Tax affects transcriptional activation mediated by the cAMP-responsive element (CRE) modulator (CREM). The CREM proteins are highly homologous to CREB, particularly in their DNA-binding domains and the kinase-inducible domain (KID), a region that interacts with the coactivator CREB-binding protein (CBP) in a phosphorylation-dependent manner. Despite this similarity, most CREM isoforms are transcriptional repressors. CREMα lacks the glutamine- rich domains found in CREB that are essential for transcriptional activation. We show that the normally repressive CREMα activates the HTLV-1 and cellular CREs in the presence of Tax; activation of the viral element is phosphorylation-independent, and activation of the cellular CRE is phosphorylation-dependent. CREMΔ(C-G) lacks both the KID and the glutamine- rich regions. This isoform activates the HTLV-1 long terminal repeat in a phosphorylation-independent manner, but does not activate the cellular CRE. This study suggests that Tax, interacting with the basic/zipper region of CREM, recruits CBP to the viral promoter. Tax activation of the cellular CRE depends on the KID and its ability to interact with CBP in a phosphorylation- dependent manner.",
author = "Laurance, {Megan E.} and Kwok, {Roland P S} and Huang, {Mary S.} and Richards, {Jane P.} and James Lundblad and Richard Goodman",
year = "1997",
doi = "10.1074/jbc.272.5.2646",
language = "English (US)",
volume = "272",
pages = "2646--2651",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "5",

}

TY - JOUR

T1 - Differential activation of viral and cellular promoters by human T-cell lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms

AU - Laurance, Megan E.

AU - Kwok, Roland P S

AU - Huang, Mary S.

AU - Richards, Jane P.

AU - Lundblad, James

AU - Goodman, Richard

PY - 1997

Y1 - 1997

N2 - We have previously proposed that cAMP-responsive element-binding protein (CREB) activity is stimulated by human T-cell lymphotropic virus-1 (HTLV-1) Tax through two mechanisms that are differentially dependent upon CREB phosphorylation. We have tested this model by examining how Tax affects transcriptional activation mediated by the cAMP-responsive element (CRE) modulator (CREM). The CREM proteins are highly homologous to CREB, particularly in their DNA-binding domains and the kinase-inducible domain (KID), a region that interacts with the coactivator CREB-binding protein (CBP) in a phosphorylation-dependent manner. Despite this similarity, most CREM isoforms are transcriptional repressors. CREMα lacks the glutamine- rich domains found in CREB that are essential for transcriptional activation. We show that the normally repressive CREMα activates the HTLV-1 and cellular CREs in the presence of Tax; activation of the viral element is phosphorylation-independent, and activation of the cellular CRE is phosphorylation-dependent. CREMΔ(C-G) lacks both the KID and the glutamine- rich regions. This isoform activates the HTLV-1 long terminal repeat in a phosphorylation-independent manner, but does not activate the cellular CRE. This study suggests that Tax, interacting with the basic/zipper region of CREM, recruits CBP to the viral promoter. Tax activation of the cellular CRE depends on the KID and its ability to interact with CBP in a phosphorylation- dependent manner.

AB - We have previously proposed that cAMP-responsive element-binding protein (CREB) activity is stimulated by human T-cell lymphotropic virus-1 (HTLV-1) Tax through two mechanisms that are differentially dependent upon CREB phosphorylation. We have tested this model by examining how Tax affects transcriptional activation mediated by the cAMP-responsive element (CRE) modulator (CREM). The CREM proteins are highly homologous to CREB, particularly in their DNA-binding domains and the kinase-inducible domain (KID), a region that interacts with the coactivator CREB-binding protein (CBP) in a phosphorylation-dependent manner. Despite this similarity, most CREM isoforms are transcriptional repressors. CREMα lacks the glutamine- rich domains found in CREB that are essential for transcriptional activation. We show that the normally repressive CREMα activates the HTLV-1 and cellular CREs in the presence of Tax; activation of the viral element is phosphorylation-independent, and activation of the cellular CRE is phosphorylation-dependent. CREMΔ(C-G) lacks both the KID and the glutamine- rich regions. This isoform activates the HTLV-1 long terminal repeat in a phosphorylation-independent manner, but does not activate the cellular CRE. This study suggests that Tax, interacting with the basic/zipper region of CREM, recruits CBP to the viral promoter. Tax activation of the cellular CRE depends on the KID and its ability to interact with CBP in a phosphorylation- dependent manner.

UR - http://www.scopus.com/inward/record.url?scp=0031030101&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031030101&partnerID=8YFLogxK

U2 - 10.1074/jbc.272.5.2646

DO - 10.1074/jbc.272.5.2646

M3 - Article

C2 - 9006899

AN - SCOPUS:0031030101

VL - 272

SP - 2646

EP - 2651

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 5

ER -