CCAAT/Enhancer-Binding Protein α Is a Physiological Regulator of Prolactin Gene Expression1.

The sequence −101/−92 of the PRL promoter has been shown to be essential for both basal and hormone-increased PRL gene transcription. It is important to identify transcription factors that bind to this sequence if we are to understand the regulation of the PRL gene. Nuclear proteins, metabolically labeled with 35S were used in gel mobility shift experiments to examine which protein(s) binds to this region of the PRL promoter. An abundant 43-kDa protein binds to the PRL promoter at −106/−87. Two 43-kDa transcription factors were identified in cytosolic extracts of GH4 cells, CCAAT enhancer-binding protein α (C/EBPα) and cAMP response element-binding protein. Both of these bind to the PRL promoter, and both were present in GH4 cell nuclear extract, but only C/EBPα was definitively identified in complexes with PRL promoter DNA. Expression of C/EBPα increased basal PRL gene expression almost 6-fold, whereas expression of Chop10 that can act as an inhibitor of C/EBPα reduced the basal activity of the PRL promo...

[1]  K. K. Jacob,et al.  The EGF response element in the prolactin promoter , 1999, Molecular and Cellular Endocrinology.

[2]  R. Day,et al.  Visualization of Pit-1 transcription factor interactions in the living cell nucleus by fluorescence resonance energy transfer microscopy. , 1998, Molecular endocrinology.

[3]  O. MacDougald,et al.  Signaling Pathways through Which Insulin Regulates CCAAT/Enhancer Binding Protein α (C/EBPα) Phosphorylation and Gene Expression in 3T3-L1 Adipocytes , 1997, The Journal of Biological Chemistry.

[4]  Michael C. Ostrowski,et al.  GHF-1/Pit-1 Functions as a Cell-specific Integrator of Ras Signaling by Targeting the Ras Pathway to a Composite Ets-1/GHF-1 Response Element* , 1996, The Journal of Biological Chemistry.

[5]  K. K. Jacob,et al.  GABP Mediates Insulin-increased Prolactin Gene Transcription (*) , 1996, The Journal of Biological Chemistry.

[6]  K. K. Jacob,et al.  A Consensus Insulin Response Element Is Activated by an ETS-related Transcription Factor (*) , 1995, The Journal of Biological Chemistry.

[7]  R. Maurer,et al.  A Composite Ets/Pit-1 Binding Site in the Prolactin Gene Can Mediate Transcriptional Responses to Multiple Signal Transduction Pathways (*) , 1995, The Journal of Biological Chemistry.

[8]  J. Burch,et al.  DNA-binding specificity of the PAR basic leucine zipper protein VBP partially overlaps those of the C/EBP and CREB/ATF families and is influenced by domains that flank the core basic region , 1995, Molecular and cellular biology.

[9]  A. Gutierrez-Hartmann,et al.  Reconstitution of protein kinase A regulation of the rat prolactin promoter in HeLa nonpituitary cells: identification of both GHF-1/Pit-1-dependent and -independent mechanisms. , 1995, Molecular endocrinology.

[10]  F. Bosch,et al.  Insulin Inhibits Liver Expression of the CCAAT/Enhancer-Binding Protein β , 1995, Diabetes.

[11]  J. Habener,et al.  Impaired cyclic AMP-dependent phosphorylation renders CREB a repressor of C/EBP-induced transcription of the somatostatin gene in an insulinoma cell line , 1995, Molecular and cellular biology.

[12]  K. K. Jacob,et al.  The insulin and cAMP response elements of the prolactin gene are overlapping sequences. , 1994, The Journal of biological chemistry.

[13]  W. Liao,et al.  Induction of the mouse serum amyloid A3 gene by cytokines requires both C/EBP family proteins and a novel constitutive nuclear factor , 1994, Molecular and cellular biology.

[14]  K. Kim,et al.  Roles of CCAAT/enhancer-binding protein and its binding site on repression and derepression of acetyl-CoA carboxylase gene. , 1994, The Journal of biological chemistry.

[15]  J. Uitto,et al.  Differential cytokine regulation of type I and type VII collagen gene expression in cultured human dermal fibroblasts. , 1994, The Journal of biological chemistry.

[16]  M. Plumb,et al.  C/EBP, NF-kappa B, and c-Ets family members and transcriptional regulation of the cell-specific and inducible macrophage inflammatory protein 1 alpha immediate-early gene , 1993, Molecular and cellular biology.

[17]  M. Harbers,et al.  Identification and analysis of all components of a gel retardation assay by combination with immunoblotting. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Moorman,et al.  Relative roles of CCAAT/enhancer-binding protein beta and cAMP regulatory element-binding protein in controlling transcription of the gene for phosphoenolpyruvate carboxykinase (GTP). , 1993, The Journal of biological chemistry.

[19]  A. Gutierrez-Hartmann,et al.  Cyclic adenosine 3',5'-monophosphate activation of the rat prolactin promoter is restricted to the pituitary-specific cell type. , 1992, Molecular endocrinology.

[20]  J. Martial,et al.  Binding of a 100-kDa ubiquitous factor to the human prolactin promoter is required for its basal and hormone-regulated activity. , 1992, European journal of biochemistry.

[21]  F. Stanley.  An element in the prolactin promoter mediates the stimulatory effect of insulin on transcription of the prolactin gene. , 1992, The Journal of biological chemistry.

[22]  R. Maurer,et al.  Characterization of a non-tissue-specific, 3',5'-cyclic adenosine monophosphate-responsive element in the proximal region of the rat prolactin gene. , 1992, Molecular endocrinology.

[23]  D. Ron,et al.  CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. , 1992, Genes & development.

[24]  J. Martial,et al.  Transcriptional induction of the human prolactin gene by cAMP requires two cis-acting elements and at least the pituitary-specific factor Pit-1. , 1991, The Journal of biological chemistry.

[25]  R. Umek,et al.  Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. , 1991, Genes & development.

[26]  R. Kageyama,et al.  Molecular characterization of transcription factors that bind to the cAMP responsive region of the substance P precursor gene. cDNA cloning of a novel C/EBP-related factor. , 1991, The Journal of biological chemistry.

[27]  J. Liu,et al.  The role of the CCAAT/enhancer-binding protein in the transcriptional regulation of the gene for phosphoenolpyruvate carboxykinase (GTP) , 1990, Molecular and cellular biology.

[28]  S. Koike,et al.  Both Pit-1 and the estrogen receptor are required for estrogen responsiveness of the rat prolactin gene. , 1990, Molecular endocrinology.

[29]  F. Stanley.  Transcriptional regulation of prolactin gene expression by thyroid hormone--alternate suppression and stimulation in different GH cell lines. , 1989, Molecular endocrinology.

[30]  S. McKnight,et al.  CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells. , 1989, Genes & development.

[31]  F. Stanley.  Stimulation of prolactin gene expression by insulin. , 1988, The Journal of biological chemistry.

[32]  M. Treacy,et al.  Tissue specific trans‐acting factor interaction with proximal rat prolactin gene promoter sequences. , 1988, The EMBO journal.

[33]  E. Barnard,et al.  Purification of the neurotensin receptor from bovine brain. , 1988, The Journal of biological chemistry.

[34]  R. Maurer,et al.  Identification of an estrogen-responsive element from the 5'-flanking region of the rat prolactin gene , 1987, Molecular and cellular biology.

[35]  Z. D. Sharp,et al.  Reconstitution of cell-type-specific transcription of the rat prolactin gene in vitro , 1987, Molecular and cellular biology.

[36]  S. Loukin,et al.  Selective transcription and DNase I protection of the rat prolactin gene by GH3 pituitary cell-free extracts. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[37]  U. Schibler,et al.  Tissue-specific in vitro transcription from the mouse albumin promoter , 1986, Cell.

[38]  H. Samuels,et al.  Depletion of L-3,5,3'-triiodothyronine and L-thyroxine in euthyroid calf serum for use in cell culture studies of the action of thyroid hormone. , 1979, Endocrinology.

[39]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[40]  F. Schaufele.  CCAAT/Enhancer-binding Protein (cid:97) Activation of the Rat Growth Hormone Promoter in Pituitary Progenitor GHFT1-5 Cells* , 1996 .