Linked Life Data

18337589

Source:http://linkedlifedata.com/resource/pubmed/id/18337589

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-5-30
pubmed:abstractText
Several posttranslational modifications including phosphorylation have been detected on the glucocorticoid receptor (GR). However, the interdependence and combinatorial regulation of these modifications and their role in GR functions are poorly understood. We studied the effects of c-Jun N-terminal kinase (JNK)-dependent phosphorylation of GR on its sumoylation status and the impact that these modifications have on GR transcriptional activity. GR is targeted for phosphorylation at serine 246 (S246) by the JNK protein family in a rapid and transient manner. The levels of S246 phosphorylation of endogenous GR increased significantly in cells treated with UV radiation that activates JNK. S246 GR phosphorylation by JNK facilitated subsequent GR sumoylation at lysines 297 and 313. GR sumoylation increased with JNK activation and was inhibited in cells treated with JNK inhibitor. GR sumoylation in cells with activated JNK was mediated preferentially by small ubiquitin-like modifier (SUMO)2 rather than SUMO1. An increase in GR transcriptional activity was observed after inhibition of JNK or SUMO pathways and suppression of GR transcriptional activity after activation of both pathways in cells transfected with GR-responsive reporter genes. Endogenous GR transcriptional activity was inhibited on endogenous target genes IGF binding protein (IGFBP) and glucocorticoid-induced leucine zipper (GILZ) when JNK and SUMO pathways were induced individually or simultaneously. Activation of both of these signals inhibited GR-mediated regulation of human inhibitor of apoptosis gene (hIAP), whereas simultaneous activation had no effect. We conclude that phosphorylation aids GR sumoylation and that cross talk of JNK and SUMO pathways fine tune GR transcriptional activity in a target gene-specific manner, thereby modulating the hormonal response of cells exposed to stress.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1331-44
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18337589-Animals, pubmed-meshheading:18337589-COS Cells, pubmed-meshheading:18337589-Cercopithecus aethiops, pubmed-meshheading:18337589-Dexamethasone, pubmed-meshheading:18337589-Humans, pubmed-meshheading:18337589-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:18337589-Models, Biological, pubmed-meshheading:18337589-Phosphorylation, pubmed-meshheading:18337589-Protein Processing, Post-Translational, pubmed-meshheading:18337589-Rats, pubmed-meshheading:18337589-Receptor Cross-Talk, pubmed-meshheading:18337589-Receptors, Glucocorticoid, pubmed-meshheading:18337589-Serine, pubmed-meshheading:18337589-Signal Transduction, pubmed-meshheading:18337589-Small Ubiquitin-Related Modifier Proteins, pubmed-meshheading:18337589-Transcriptional Activation, pubmed-meshheading:18337589-Tumor Cells, Cultured
pubmed:year
2008
pubmed:articleTitle
Cross talk of signaling pathways in the regulation of the glucocorticoid receptor function.
pubmed:affiliation
The University of Manchester, Oxford Road, Manchester M13 9PT, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't