title: Depletion of the cellular levels of Bag-1 proteins attenuates phorbol ester-induced downregulation of IκBα and nuclear accumulation of NF-κB.
abstract: Bag-1 consists in humans of four isoforms generated from the same RNA by alternative translation. Overexpression of single Bag-1 isoforms has identified Bag-1 as a negative regulator of action of many proteins including the glucocorticoid receptor (GR). Here we have analysed the ability of Bag-1 to regulate the transrepression function of the GR. Silencing Bag-1 expression only marginally affects the transrepression action of the GR but decreased the action of the transcription factor NF-κB. Furthermore phosphorylation and degradation of the inhibitor protein IκBα and nuclear accumulation of p65 and p50 NF-κB proteins in response to phorbol ester was attenuated following Bag-1 depletion in HeLa cells. Reconstitution of Bag-1 in depleted cells partially restored IκBα and NF-κB activation. Knock-down of Bag-1 expression also did not significantly alter GR-mediated transactivation but affected the basal transcription of some of the target genes. Thus Bag-1 proteins function as regulators of the action of selective transcription factors.
authors.affiliation: Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany. Jana.maier@kit.edu
authors.forename: Jana V
authors.initials: JV
authors.lastname: Maier
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Volz
authors.forename: Caroline
authors.initials: C
authors.lastname: Berger
authors.forename: Sandra
authors.initials: S
authors.lastname: Schneider
authors.forename: Andrew C B
authors.initials: AC
authors.lastname: Cato
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010703:Phorbol Esters / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D010703:Phorbol Esters; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha