Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1998-10-5
|
| pubmed:abstractText |
The brown fat uncoupling protein-1 (ucp-1) gene is regulated by the sympathetic nervous system, and its transcription is stimulated by norepinephrine, mainly through cAMP-mediated pathways. Overexpression of the catalytic subunit of protein kinase A stimulated a chloramphenicol acetyltransferase expression vector driven by the 4.5-kb 5'-region of the rat ucp-1 gene. Mutant deletion analysis indicated the presence of the main cAMP-regulatory element (CRE) in the proximal region between -141 and -54. This region contains an element at -139/-122 able to confer enhancer and protein kinase A (PKA)-dependent activity to the basal thymidine kinase promoter. The potency of this element was much higher in differentiated than in nondifferentiated brown adipocytes. Gel shift analyses indicated that a complex array of proteins from brown fat nuclei bind to the -139/-122 element, among which CRE-binding protein (CREB) and Jun proteins were identified. In transfected brown adipocytes, c-Jun was a negative regulator of basal and PKA-induced transcription from the ucp-1 promoter acting through this proximal CRE region. A double-point mutation in the -139/-122 element abolished both PKA- and c-Jun-dependent regulation through this site, and overexpression of CREB blocked c-Jun repression. Thus, an opposite action of these two transcription factors on the -139/-122 CRE is proposed. c-Jun content in brown adipocytes differentiating in culture correlated negatively with both ucp-1 gene expression and the acquisition of the brown adipocyte morphology. These findings indicate that c-Jun provides a molecular mechanism to repress the basal and cAMP-mediated expression of the ucp-1 gene before the differentiation of the brown adipocyte.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ion Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/mitochondrial uncoupling protein
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0888-8809
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
12
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1023-37
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:9658406-Adipocytes,
pubmed-meshheading:9658406-Adipose Tissue, Brown,
pubmed-meshheading:9658406-Animals,
pubmed-meshheading:9658406-Carrier Proteins,
pubmed-meshheading:9658406-Cell Differentiation,
pubmed-meshheading:9658406-Cyclic AMP,
pubmed-meshheading:9658406-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:9658406-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:9658406-Enhancer Elements, Genetic,
pubmed-meshheading:9658406-Gene Expression,
pubmed-meshheading:9658406-Gene Expression Regulation,
pubmed-meshheading:9658406-Ion Channels,
pubmed-meshheading:9658406-Membrane Proteins,
pubmed-meshheading:9658406-Mice,
pubmed-meshheading:9658406-Mitochondrial Proteins,
pubmed-meshheading:9658406-Norepinephrine,
pubmed-meshheading:9658406-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:9658406-Rats,
pubmed-meshheading:9658406-Recombinant Fusion Proteins,
pubmed-meshheading:9658406-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:9658406-Transfection
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Dominant negative regulation by c-Jun of transcription of the uncoupling protein-1 gene through a proximal cAMP-regulatory element: a mechanism for repressing basal and norepinephrine-induced expression of the gene before brown adipocyte differentiation.
|
| pubmed:affiliation |
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Spain.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|