Nur77 induction and activation are necessary for interleukin-1 stimulation of proopiomelanocortin in AtT-20 corticotrophs.
Nur77 and Nurr1 are critical for proopiomelanocortin (POMC) regulation by corticotrophin releasing hormone (CRH) in corticotrophs. We analyze the regulation and activity of Nur77 by interleukin (IL)-1 in AtT-20 corticotrophic cells and its consequences on POMC regulation. IL-1 induces Nur77 and not Nurr1 mRNA and shows an increased transcriptional activity on the NurRE site, an effect dependent of p38 protein kinase activity. A NurRE mutation abrogates POMC promoter transcription by IL-1 and a stable AtT-20 clone overexpressing a dominant negative form of Nur77 is unresponsive to IL-1-dependent POMC induction and adrenocorticotrophin (ACTH) secretion. These results demonstrate that Nur77 is essential for POMC stimulation by IL-1 in corticotrophs.
Kovalovsky
Damian
D
Departamento de Fisiología y Biología Molecular, FCEN, Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina.
Paez Pereda
Marcelo
M
Labeur
Marta
M
Renner
Ulrich
U
Holsboer
Florian
F
Stalla
Günter K
GK
Arzt
Eduardo
E
D000818:Animals; D045744:Cell Line, Tumor; D002999:Clone Cells; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010911:Pituitary Neoplasms / Q000473:pathology; D011333:Pro-Opiomelanocortin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D020218:Response Elements / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases
D004268:DNA-Binding Proteins; D007375:Interleukin-1; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases