Linked Life Data

11092886

Source:http://linkedlifedata.com/resource/pubmed/id/11092886

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-5-23
pubmed:abstractText
Cyclic AMP-response element modulator alpha (CREMalpha) is a transcription factor that is highly related to cAMP-response element-binding protein (CREB) but represses cAMP-induced gene expression from simple artificial promoters containing a cAMP-response element (CRE). CREMalpha lacks two glutamine-rich Q regions that, in CREB, are thought to be necessary for transcriptional activation. Nevertheless, protein kinase A stimulation induces CREMalpha to activate the complex native promoter in the phosphoenolpyruvate carboxykinase (PEPCK) gene. To study this phenomenon in the absence of protein kinase A stimulation, we introduced a mutation into CREMalpha to allow constitutive binding to the coactivator CREB-binding protein. This mutant, CREMalpha(DIEDML), constitutively activated the PEPCK promoter. By engineering the leucine zipper regions of CREMalpha(DIEDML) and CREB(DIEDML) to direct their patterns of dimerization, we found that only CREMalpha(DIEDML) homodimers fully activated the PEPCK promoter. By using a series of deletion and block mutants of the PEPCK promoter, we found that activation by CREMalpha(DIEDML) depended on the CRE and two CCAAT/enhancer-binding protein (C/EBP) sites. A dominant negative inhibitor of C/EBP, A-C/EBP, suppressed activation by CREMalpha(DIEDML). Furthermore, a GAL4-C/EBPalpha fusion protein and CREMalpha(DIEDML) cooperatively activated a promoter containing three GAL4 sites and the PEPCK CRE. Thus, we propose that the C/EBP sites in the PEPCK promoter allow CREMalpha to activate transcription despite its lack of Q regions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2992-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11092886-Amino Acid Motifs, pubmed-meshheading:11092886-Amino Acid Sequence, pubmed-meshheading:11092886-Amino Acid Substitution, pubmed-meshheading:11092886-Binding Sites, pubmed-meshheading:11092886-Cyclic AMP Response Element Modulator, pubmed-meshheading:11092886-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:11092886-DNA-Binding Proteins, pubmed-meshheading:11092886-Humans, pubmed-meshheading:11092886-Molecular Sequence Data, pubmed-meshheading:11092886-Mutation, pubmed-meshheading:11092886-Phosphoenolpyruvate Carboxykinase (ATP), pubmed-meshheading:11092886-Repressor Proteins, pubmed-meshheading:11092886-Sequence Homology, Amino Acid, pubmed-meshheading:11092886-Transcriptional Activation, pubmed-meshheading:11092886-Transfection, pubmed-meshheading:11092886-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Cooperative mechanism of transcriptional activation by a cyclic AMP-response element modulator alpha mutant containing a motif for constitutive binding to CREB-binding protein.
pubmed:affiliation
Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.