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Science 17 April 1992:
Vol. 256. no. 5055, pp. 370 - 373
DOI: 10.1126/science.256.5055.370
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Articles

Calcium-Regulated Phosphorylation Within the Leucine Zipper of C/EBPbeta

Michael Wegner 1, Zhaodan Cao 2, and Michael G. Rosenfeld 1

1 Eukaryotic Regulatory Biology Program and Howard Hughes Medical Institute, Cellular and Molecular Medicine Building, University of California, San Diego, La Jolla, CA 92093-0648
2 Department of Embryology, Howard Hughes Research Laboratories, Carnegie Institution of Washington, Baltimore, MD 21210

Alterations in intracellular calcium levels activate several signal transduction pathways resulting in distinct patterns of gene expression. Here, a pathway for calcium-mediated signals is demonstrated that involves C/EBPbeta, a member of the bZip family of transcription factors. In pituitary cells C/EBPbeta was phosphorylated in response to increased intracellular calcium concentrations as a consequence of the activation of a calcium-calmodulin— dependent protein kinase. Phosphorylation of serine at position 276 within the leucine zipper of C/EBPbeta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBPbeta.


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Protein Synthesis Inhibitors Exhibit a Nonspecific Effect on Phenobarbital-inducible Cytochome P450 Gene Expression in Primary Rat Hepatocytes.
J. S. Sidhu and C. J. Omiecinski (1998)
J. Biol. Chem. 273, 4769-4775
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R. R. White, Y.-G. Kwon, M. Taing, D. S. Lawrence, and A. M. Edelman (1998)
J. Biol. Chem. 273, 3166-3172
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R. Chinery, J. A. Brockman, D. T. Dransfield, and R. J. Coffey (1997)
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Pancreatic beta -Cell-specific Repression of Insulin Gene Transcription by CCAAT/Enhancer-binding Protein beta . INHIBITORY INTERACTIONS WITH BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR E47.
M. Lu, J. Seufert, and J. F. Habener (1997)
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An Okadaic Acid-Sensitive Pathway Involved in the Phenobarbital-Mediated Induction of CYP2B Gene Expression in Primary Rat Hepatocyte Cultures.
J. S. Sidhu and C. J. Omiecinski (1997)
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D. G. Tenen, R. Hromas, J. D. Licht, and D.-E. Zhang (1997)
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GABP Cooperates With c-Myb and C/EBP to Activate the Neutrophil Elastase Promoter.
I. Nuchprayoon, C. P. Simkevich, M. Luo, A. D. Friedman, and A. G. Rosmarin (1997)
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L. M. Gault and R. E. Siegel (1997)
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T. Gotoh, S. Chowdhury, M. Takiguchi, and M. Mori (1997)
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H.-y. Wang, M. S. Goligorsky, and C. C. Malbon (1997)
J. Biol. Chem. 272, 1817-1821
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Modulation of Calcium Channels in Human Erythroblasts by Erythropoietin.
J. Y. Cheung, X.-Q. Zhang, K. Bokvist, D. L. Tillotson, and B. A. Miller (1997)
Blood 89, 92-100
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Regulation of CCAAT/Enhancer-binding Protein Family Members by Stimulation of Glutamate Receptors in Cultured Rat Cortical Astrocytes.
S. Yano, K. Fukunaga, M. Takiguchi, Y. Ushio, M. Mori, and E. Miyamoto (1996)
J. Biol. Chem. 271, 23520-23527
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C/EBP-beta /LAP Controls Down-regulation of Albumin Gene Transcription during Liver Regeneration.
C. Trautwein, T. Rakemann, A. Pietrangelo, J. Plumpe, G. Montosi, and M. P. Manns (1996)
J. Biol. Chem. 271, 22262-22270
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Light-Induced Phase Shifting of the Circadian Conidiation Rhythm Is Inhibited by Calmodulin Antagonists in Neurospora crassa.
Y. Sadakane and H. Nakashima (1996)
J Biol Rhythms 11, 234-240
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CCAAT/Enhancer-binding Protein alpha Activation of the Rat Growth Hormone Promoter in Pituitary Progenitor GHFT1-5 Cells.
F. Schaufele and F. Schaufele (1996)
J. Biol. Chem. 271, 21484-21489
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Tumor Necrosis Factor alpha Promotes Nuclear Localization of Cytokine-inducible CCAAT/Enhancer Binding Protein Isoforms in Hepatocytes.
M. Yin, S. Q. Yang, H. Z. Lin, M. D. Lane, S. Chatterjee, and A. M. Diehl (1996)
J. Biol. Chem. 271, 17974-17978
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Mechanisms for Inducible Control of Angiotensinogen Gene Transcription.
A. R. Brasier and J. Li (1996)
Hypertension 27, 465-475
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In Situ Ca[IMAGE] Dependence for Activation of Ca[IMAGE]/Calmodulin- dependent Protein Kinase II in Vascular Smooth Muscle Cells.
S. T. Abraham, H. Benscoter, C. M. Schworer, and H. A. Singer (1996)
J. Biol. Chem. 271, 2506-2513
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Inositol 1,4,5-Trisphosphate Receptor Is Located to the Inner Nuclear Membrane Vindicating Regulation of Nuclear Calcium Signaling by Inositol 1,4,5-Trisphosphate.
J.-P. Humbert, N. Matter, J.-C. Artault, P. Köppler, and A. N. Malviya (1996)
J. Biol. Chem. 271, 478-485
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cAMP Activation of CAAT Enhancer-binding Protein-beta Gene Expression and Promoter I of Acetyl-CoA Carboxylase.
H.-J. Tae, S. Zhang, and K.-H. Kim (1995)
J. Biol. Chem. 270, 21487-21494
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Transcription Stimulation of the Fas-encoding Gene by Nuclear Factor for Interleukin-6 Expression upon Influenza Virus Infection.
N. Wada, M. Matsumura, Y. Ohba, N. Kobayashi, T. Takizawa, and Y. Nakanishi (1995)
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Genes & Dev. 8, 2781-2791
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The alternatively initiated c-Myc proteins differentially regulate transcription through a noncanonical DNA-binding site..
S R Hann, M Dixit, R C Sears, and L Sealy (1994)
Genes & Dev. 8, 2441-2452
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Insulin Suppresses Transactivation by CAAT/Enhancer-binding Proteins beta (C/EBPbeta ). SIGNALING TO p300/CREB-BINDING PROTEIN BY PROTEIN KINASE B DISRUPTS INTERACTION WITH THE MAJOR ACTIVATION DOMAIN OF C/EBPbeta.
S. Guo, S. B. Cichy, X. He, Q. Yang, M. Ragland, A. K. Ghosh, P. F. Johnson, and T. G. Unterman (2001)
J. Biol. Chem. 276, 8516-8523
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Interleukin-6-induced Tethering of STAT3 to the LAP/C/EBPbeta Promoter Suggests a New Mechanism of Transcriptional Regulation by STAT3.
M. Niehof, K. Streetz, T. Rakemann, S. C. Bischoff, M. P. Manns, F. Horn, and C. Trautwein (2001)
J. Biol. Chem. 276, 9016-9027
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Regulated Nuclear-Cytoplasmic Localization of CCAAT/ Enhancer-binding Protein delta in Osteoblasts.
J. Billiard, Y. Umayahara, K. Wiren, M. Centrella, T. L. McCarthy, and P. Rotwein (2001)
J. Biol. Chem. 276, 15354-15361
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Growth Hormone Regulates Phosphorylation and Function of CCAAT/Enhancer-binding Protein beta by Modulating Akt and Glycogen Synthase Kinase-3.
G. Piwien-Pilipuk, D. Van Mater, S. E. Ross, O. A. MacDougald, and J. Schwartz (2001)
J. Biol. Chem. 276, 19664-19671
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Selective Suppression of CCAAT/Enhancer-binding Protein beta Binding and Cyclooxygenase-2 Promoter Activity by Sodium Salicylate in Quiescent Human Fibroblasts.
M. A. Saunders, L. Sansores-Garcia, D. W. Gilroy, and K. K. Wu (2001)
J. Biol. Chem. 276, 18897-18904
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Localization of the Cyclic ADP-ribose-dependent Calcium Signaling Pathway in Hepatocyte Nucleus.
K. M. Khoo, M.-K. Han, J. B. Park, S. W. Chae, U.-H. Kim, H. C. Lee, B. H. Bay, and C. F. Chang (2000)
J. Biol. Chem. 275, 24807-24817
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The C/EBP bZIP Domain Can Mediate Lipopolysaccharide Induction of the Proinflammatory Cytokines Interleukin-6 and Monocyte Chemoattractant Protein-1.
H.-M. Hu, Q. Tian, M. Baer, C. J. Spooner, S. C. Williams, P. F. Johnson, and R. C. Schwartz (2000)
J. Biol. Chem. 275, 16373-16381
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Cellular Signaling through Multifunctional Ca2+/Calmodulin-dependent Protein Kinase II.
T. R. Soderling, B. Chang, and D. Brickey (2001)
J. Biol. Chem. 276, 3719-3722
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