C/EBP2 mediates growth hormone-regulated expression of multiple target genes
Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired respons...
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todo:paper_08888809_v25_n4_p681_Cui2023-10-03T15:41:10Z C/EBP2 mediates growth hormone-regulated expression of multiple target genes Cui, T.X. Lin, G. Lapensee, C.R. Calinescu, A.-A. Rathore, M. Streeter, C. Piwien-Pilipuk, G. Lanning, N. Jin, H. Carter-Su, C. Qin, Z.S. Schwartz, J. CCAAT enhancer binding protein beta cyclic AMP responsive element binding protein growth hormone mitogen activated protein kinase protein p300 short hairpin RNA STAT protein 1,3 butadiene derivative 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene Cebpb protein, mouse histone acetyltransferase PCAF nitrile small interfering RNA animal cell article early response gene enzyme activation gene activation gene expression gene expression regulation gene targeting human human cell mouse nonhuman oncogene c fos priority journal promoter region protein phosphorylation animal cell line chromatin immunoprecipitation Cricetulus DNA responsive element genetics hamster immunoblotting metabolism mutation oncogene phosphorylation polymerase chain reaction signal transduction transcription initiation Animals Butadienes CCAAT-Enhancer-Binding Protein-beta Cell Line Chromatin Immunoprecipitation Cricetinae Cricetulus Extracellular Signal-Regulated MAP Kinases Gene Expression Regulation Genes, fos Growth Hormone Immunoblotting Mice Mutation Nitriles p300-CBP Transcription Factors Phosphorylation Polymerase Chain Reaction Promoter Regions, Genetic Response Elements RNA, Small Interfering Signal Transduction Transcriptional Activation Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression. In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126. Thus, induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH. © 2011 by The Endocrine Society. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_08888809_v25_n4_p681_Cui |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
CCAAT enhancer binding protein beta cyclic AMP responsive element binding protein growth hormone mitogen activated protein kinase protein p300 short hairpin RNA STAT protein 1,3 butadiene derivative 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene Cebpb protein, mouse histone acetyltransferase PCAF nitrile small interfering RNA animal cell article early response gene enzyme activation gene activation gene expression gene expression regulation gene targeting human human cell mouse nonhuman oncogene c fos priority journal promoter region protein phosphorylation animal cell line chromatin immunoprecipitation Cricetulus DNA responsive element genetics hamster immunoblotting metabolism mutation oncogene phosphorylation polymerase chain reaction signal transduction transcription initiation Animals Butadienes CCAAT-Enhancer-Binding Protein-beta Cell Line Chromatin Immunoprecipitation Cricetinae Cricetulus Extracellular Signal-Regulated MAP Kinases Gene Expression Regulation Genes, fos Growth Hormone Immunoblotting Mice Mutation Nitriles p300-CBP Transcription Factors Phosphorylation Polymerase Chain Reaction Promoter Regions, Genetic Response Elements RNA, Small Interfering Signal Transduction Transcriptional Activation |
spellingShingle |
CCAAT enhancer binding protein beta cyclic AMP responsive element binding protein growth hormone mitogen activated protein kinase protein p300 short hairpin RNA STAT protein 1,3 butadiene derivative 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene Cebpb protein, mouse histone acetyltransferase PCAF nitrile small interfering RNA animal cell article early response gene enzyme activation gene activation gene expression gene expression regulation gene targeting human human cell mouse nonhuman oncogene c fos priority journal promoter region protein phosphorylation animal cell line chromatin immunoprecipitation Cricetulus DNA responsive element genetics hamster immunoblotting metabolism mutation oncogene phosphorylation polymerase chain reaction signal transduction transcription initiation Animals Butadienes CCAAT-Enhancer-Binding Protein-beta Cell Line Chromatin Immunoprecipitation Cricetinae Cricetulus Extracellular Signal-Regulated MAP Kinases Gene Expression Regulation Genes, fos Growth Hormone Immunoblotting Mice Mutation Nitriles p300-CBP Transcription Factors Phosphorylation Polymerase Chain Reaction Promoter Regions, Genetic Response Elements RNA, Small Interfering Signal Transduction Transcriptional Activation Cui, T.X. Lin, G. Lapensee, C.R. Calinescu, A.-A. Rathore, M. Streeter, C. Piwien-Pilipuk, G. Lanning, N. Jin, H. Carter-Su, C. Qin, Z.S. Schwartz, J. C/EBP2 mediates growth hormone-regulated expression of multiple target genes |
topic_facet |
CCAAT enhancer binding protein beta cyclic AMP responsive element binding protein growth hormone mitogen activated protein kinase protein p300 short hairpin RNA STAT protein 1,3 butadiene derivative 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene Cebpb protein, mouse histone acetyltransferase PCAF nitrile small interfering RNA animal cell article early response gene enzyme activation gene activation gene expression gene expression regulation gene targeting human human cell mouse nonhuman oncogene c fos priority journal promoter region protein phosphorylation animal cell line chromatin immunoprecipitation Cricetulus DNA responsive element genetics hamster immunoblotting metabolism mutation oncogene phosphorylation polymerase chain reaction signal transduction transcription initiation Animals Butadienes CCAAT-Enhancer-Binding Protein-beta Cell Line Chromatin Immunoprecipitation Cricetinae Cricetulus Extracellular Signal-Regulated MAP Kinases Gene Expression Regulation Genes, fos Growth Hormone Immunoblotting Mice Mutation Nitriles p300-CBP Transcription Factors Phosphorylation Polymerase Chain Reaction Promoter Regions, Genetic Response Elements RNA, Small Interfering Signal Transduction Transcriptional Activation |
description |
Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression. In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126. Thus, induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH. © 2011 by The Endocrine Society. |
format |
JOUR |
author |
Cui, T.X. Lin, G. Lapensee, C.R. Calinescu, A.-A. Rathore, M. Streeter, C. Piwien-Pilipuk, G. Lanning, N. Jin, H. Carter-Su, C. Qin, Z.S. Schwartz, J. |
author_facet |
Cui, T.X. Lin, G. Lapensee, C.R. Calinescu, A.-A. Rathore, M. Streeter, C. Piwien-Pilipuk, G. Lanning, N. Jin, H. Carter-Su, C. Qin, Z.S. Schwartz, J. |
author_sort |
Cui, T.X. |
title |
C/EBP2 mediates growth hormone-regulated expression of multiple target genes |
title_short |
C/EBP2 mediates growth hormone-regulated expression of multiple target genes |
title_full |
C/EBP2 mediates growth hormone-regulated expression of multiple target genes |
title_fullStr |
C/EBP2 mediates growth hormone-regulated expression of multiple target genes |
title_full_unstemmed |
C/EBP2 mediates growth hormone-regulated expression of multiple target genes |
title_sort |
c/ebp2 mediates growth hormone-regulated expression of multiple target genes |
url |
http://hdl.handle.net/20.500.12110/paper_08888809_v25_n4_p681_Cui |
work_keys_str_mv |
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1782025741665304576 |