Linked Life Data

15308638

Source:http://linkedlifedata.com/resource/pubmed/id/15308638

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
2004-10-25
pubmed:abstractText
Expression of the nuclear retinoic acid receptor beta2 (RARbeta2) gene is often disturbed in cervical carcinoma cells. One important mechanism by which RARbeta2 can exert growth inhibitory function is based on its ability to repress the AP-1 transcription factor in a ligand-dependent manner. Because less is known about the biological effects of RARbeta in the absence of ligand, the corresponding cDNA was stably introduced into HPV18-positive HeLa cervical carcinoma cells. In the present study we describe a novel mechanism by which AP-1 becomes inactivated. Constitutive expression of nonliganded RARbeta abrogated both AP-1 binding affinity and activity by a selective degradation of the c-Jun protein as major dimerization partner, without substitution by other members of the Jun family. Blockage of the proteasomal pathway completely rescued c-Jun and reconstituted the AP-1 function. Moreover, HeLa RARbeta2 clones treated either with tumor necrosis factor-alpha or transfected with a constitutive active upstream mitogen-activated protein kinase (MEKK1Delta) also resulted in c-Jun phosphorylation and restoration of AP-1 affinity and functionality similar to that found in nontransfected parental HeLa cells. These data revealed an important cross-talk between trans-repression of AP-1 and nonliganded RARbeta in human papillomavirus-positive cells. Because AP-1 activity was not irreversibly disturbed, but could be switched on through activation of the Jun N-terminal kinase pathway, a model for the transient activation of AP-1 even in the presence of RARbeta as repressor is suggested.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins, http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/MAP3K1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PSMD14 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1, http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci..., http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor beta
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
45408-16
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Ectopic expression of nonliganded retinoic acid receptor beta abrogates AP-1 activity by selective degradation of c-Jun in cervical carcinoma cells.
pubmed:affiliation
Angewandte Tumorvirologie, Abteilung Virale Transformationsmechanismen, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
pubmed:publicationType
Journal Article