The glucocorticoid receptor is associated with the RNA-binding nuclear matrix protein hnRNP U.
The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that is able to modulate gene activity by binding to its response element, interacting with other transcription factors, and contacting several accessory proteins such as coactivators. Here we show that GRIP120, one of the factors we have identified to interact with the glucocorticoid receptor, is identical to the heterogeneous nuclear ribonucleoprotein U (hnRNP U), a nuclear matrix protein binding to RNA as well as to scaffold attachment regions. GR.hnRNP U complexes were identified by blotting and coimmunoprecipitation. The subnuclear distribution of GR and hnRNP U was characterized by indirect immunofluorescent labeling and confocal laser microscopy demonstrating a colocalization of both proteins. Using a nuclear transport-deficient deletion of hnRNP U, nuclear translocation was seen to be dependent on GR and dexamethasone. Transient transfections were used to identify possible interaction domains. Overexpressed hnRNP U interfered with glucocorticoid induction, and the COOH-terminal domains of both proteins were sufficient in mediating the transcriptional interference. A possible functional role for this GR binding-protein in addition to its binding to the nuclear matrix, to RNA, and to scaffold attachment regions is discussed.
Eggert
M
M
Genetisches Institut der Justus-Liebig-Universität, Heinrich-Buff-Ring 58-62, D-35392, Germany.
Michel
J
J
Schneider
S
S
Bornfleth
H
H
Baniahmad
A
A
Fackelmayer
F O
FO
Schmidt
S
S
Renkawitz
R
R
D002467:Cell Nucleus / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D006367:HeLa Cells; D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000378:metabolism*; D012332:RNA, Heterogeneous Nuclear / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*
D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009363:Neoplasm Proteins; D012332:RNA, Heterogeneous Nuclear; D016601:RNA-Binding Proteins; D011965:Receptors, Glucocorticoid; D012261:Ribonucleoproteins; D003907:Dexamethasone