| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Molecular Physiology and Biophysics Vanderbilt University School of Medicine Nashville, Tennessee 37232-0615
Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the rate-limiting step of gluconeogenesis. The activity of this enzyme is controlled by several hormones, including glucocorticoids, glucagon, retinoic acid, and insulin, that principally affect the rate of transcription of the PEPCK gene. Glucocorticoids induce PEPCK gene transcription through a complex glucocorticoid response unit that consists of, from 5' to 3', accessory factor elements AF1 and AF2; two noncanonical glucocorticoid receptor-binding sites, GR1 and GR2; a third accessory factor element, AF3; and a cAMP-response element, CRE. A complete glucocorticoid response is dependent on the presence of both GR-binding sites, all three accessory elements, and the CRE. In this study we assess the relative roles of GR1 and GR2 in the context of the glucocorticoid response unit and use a combination of binding and function assays to compare GR1 and GR2 to glucocorticoid response elements (GREs) that conform closely to the consensus sequence. The relative binding affinity of GR follows the order: consensus GRE >> GR1 > GR2. Mutations that disrupt the binding of GR to GR1 result in a major reduction of the glucocorticoid response, whereas similar mutations of GR2 have a much smaller effect. Unlike the simple consensus GRE, neither GR1 nor GR2 mediate a glucocorticoid response through a heterologous promoter. The accessory elements appear to have different functional roles. AF2 is still needed for a maximal glucocorticoid response when GR1 is converted to a high-affinity GR-binding element, but AF1 and AF3 are not required.
This article has been cited by other articles:
 |
|
 |
|
  E. B. Kabotyanski, M. Huetter, W. Xian, M. Rijnkels, and J. M. Rosen Integration of Prolactin and Glucocorticoid Signaling at the {beta}-Casein Promoter and Enhancer by Ordered Recruitment of Specific Transcription Factors and Chromatin Modifiers Mol. Endocrinol., October 1, 2006; 20(10): 2355 - 2368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cassuto, K. Kochan, K. Chakravarty, H. Cohen, B. Blum, Y. Olswang, P. Hakimi, C. Xu, D. Massillon, R. W. Hanson, et al. Glucocorticoids Regulate Transcription of the Gene for Phosphoenolpyruvate Carboxykinase in the Liver via an Extended Glucocorticoid Regulatory Unit J. Biol. Chem., October 7, 2005; 280(40): 33873 - 33884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Baumann, A. Dostert, N. Novac, A. Bauer, W. Schmid, S. C. Fas, A. Krueger, T. Heinzel, S. Kirchhoff, G. Schutz, et al. Glucocorticoids inhibit activation-induced cell death (AICD) via direct DNA-dependent repression of the CD95 ligand gene by a glucocorticoid receptor dimer Blood, July 15, 2005; 106(2): 617 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Asselin-Labat, A. Biola-Vidamment, S. Kerbrat, M. Lombes, J. Bertoglio, and M. Pallardy FoxO3 Mediates Antagonistic Effects of Glucocorticoids and Interleukin-2 on Glucocorticoid-Induced Leucine Zipper Expression Mol. Endocrinol., July 1, 2005; 19(7): 1752 - 1764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shao, L. Qiao, R. C. Janssen, M. Pagliassotti, and J. E. Friedman Chronic Hyperglycemia Enhances PEPCK Gene Expression and Hepatocellular Glucose Production Via Elevated Liver Activating Protein/Liver Inhibitory Protein Ratio Diabetes, April 1, 2005; 54(4): 976 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Wang, M. K. Derynck, D. F. Nonaka, D. B. Khodabakhsh, C. Haqq, and K. R. Yamamoto From The Cover: Chromatin immunoprecipitation (ChIP) scanning identifies primary glucocorticoid receptor target genes PNAS, November 2, 2004; 101(44): 15603 - 15608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. L. Wang, B. Herzog, M. Waltner-Law, R. K. Hall, M. Shiota, and D. K. Granner The Synergistic Effect of Dexamethasone and All-trans-retinoic Acid on Hepatic Phosphoenolpyruvate Carboxykinase Gene Expression Involves the Coactivator p300 J. Biol. Chem., August 13, 2004; 279(33): 34191 - 34200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. McInnes, C. J. Kenyon, K. E. Chapman, D. E. W. Livingstone, L. J. Macdonald, B. R. Walker, and R. Andrew 5{alpha}-Reduced Glucocorticoids, Novel Endogenous Activators of the Glucocorticoid Receptor J. Biol. Chem., May 28, 2004; 279(22): 22908 - 22912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Herzog, R. K. Hall, X. L. Wang, M. Waltner-Law, and D. K. Granner Peroxisome Proliferator-Activated Receptor {gamma} Coactivator-1{alpha}, as a Transcription Amplifier, Is Not Essential for Basal and Hormone-Induced Phosphoenolpyruvate Carboxykinase Gene Expression Mol. Endocrinol., April 1, 2004; 18(4): 807 - 819. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. De Bosscher, W. Vanden Berghe, and G. Haegeman The Interplay between the Glucocorticoid Receptor and Nuclear Factor-{kappa}B or Activator Protein-1: Molecular Mechanisms for Gene Repression Endocr. Rev., August 1, 2003; 24(4): 488 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Coghlan, P. B. Jacobson, B. Lane, M. Nakane, C. W. Lin, S. W. Elmore, P. R. Kym, J. R. Luly, G. W. Carter, R. Turner, et al. A Novel Antiinflammatory Maintains Glucocorticoid Efficacy with Reduced Side Effects Mol. Endocrinol., May 1, 2003; 17(5): 860 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kucera, M. Waltner-Law, D. K. Scott, R. Prasad, and D. K. Granner A Point Mutation of the AF2 Transactivation Domain of the Glucocorticoid Receptor Disrupts Its Interaction with Steroid Receptor Coactivator 1 J. Biol. Chem., July 12, 2002; 277(29): 26098 - 26102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ma, C. Mallidis, J. Artaza, W. Taylor, N. Gonzalez-Cadavid, and S. Bhasin Characterization of 5'-regulatory region of human myostatin gene: regulation by dexamethasone in vitro Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1128 - E1136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Shen, L. M. Scearce, J. E. Brestelli, N. J. Sund, and K. H. Kaestner Foxa3 (Hepatocyte Nuclear Factor 3gamma ) Is Required for the Regulation of Hepatic GLUT2 Expression and the Maintenance of Glucose Homeostasis during a Prolonged Fast J. Biol. Chem., November 9, 2001; 276(46): 42812 - 42817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Stafford, J. C. Wilkinson, J. M. Beechem, and D. K. Granner Accessory Factors Facilitate the Binding of Glucocorticoid Receptor to the Phosphoenolpyruvate Carboxykinase Gene Promoter J. Biol. Chem., October 19, 2001; 276(43): 39885 - 39891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Wang, J. M. Stafford, D. K. Scott, C. Sutherland, and D. K. Granner The Molecular Physiology of Hepatic Nuclear Factor 3 in the Regulation of Gluconeogenesis J. Biol. Chem., May 5, 2000; 275(19): 14717 - 14721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Wang, P.-E. Strömstedt, T. Sugiyama, and D. K. Granner The Phosphoenolpyruvate Carboxykinase Gene Glucocorticoid Response Unit: Identification of the Functional Domains of Accessory Factors HNF3{beta} (Hepatic Nuclear Factor-3{beta}) and HNF4 and the Necessity of Proper Alignment of Their Cognate Binding Sites Mol. Endocrinol., April 1, 1999; 13(4): 604 - 618. [Abstract] [Full Text]
|
|
|
|
|
|
P. Leahy, D. R. Crawford, G. Grossman, R. M. Gronostajski, and R. W. Hanson CREB Binding Protein Coordinates the Function of Multiple Transcription Factors Including Nuclear Factor I to Regulate Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription J. Biol. Chem., March 26, 1999; 274(13): 8813 - 8822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Park, S. Song, C. Vinson, and W. J. Roesler Role of CCAAT Enhancer-binding Protein beta in the Thyroid Hormone and cAMP Induction of Phosphoenolpyruvate Carboxykinase Gene Transcription J. Biol. Chem., January 1, 1999; 274(1): 211 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Croniger, P. Leahy, L. Reshef, and R. W. Hanson C/EBP and the Control of Phosphoenolpyruvate Carboxykinase Gene Transcription in the Liver J. Biol. Chem., November 27, 1998; 273(48): 31629 - 31632. [Full Text] [PDF]
|
|
|
|
|
|
T. Sugiyama, D. K. Scott, J.-C. Wang, and D. K. Granner Structural Requirements of the Glucocorticoid and Retinoic Acid Response Units in the Phosphoenolpyruvate Carboxykinase Gene Promoter Mol. Endocrinol., October 1, 1998; 12(10): 1487 - 1498. [Abstract] [Full Text]
|
|
|
|
 |
|
 K.R. YAMAMOTO, B.D. DARIMONT, R.L. WAGNER, and J.A. INIGUEZ-LLUHI Building Transcriptional Regulatory Complexes: Signals and Surfaces Cold Spring Harb Symp Quant Biol, January 1, 1998; 63(0): 587 - 598. [Abstract] [PDF]
|
|
|
|
|
|
J. M. Stafford, M. Waltner-Law, and D. K. Granner Role of Accessory Factors and Steroid Receptor Coactivator 1 in the Regulation of Phosphoenolpyruvate Carboxykinase Gene Transcription by Glucocorticoids J. Biol. Chem., February 2, 2001; 276(6): 3811 - 3819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yeagley, S. Guo, T. Unterman, and P. G. Quinn Gene- and Activation-specific Mechanisms for Insulin Inhibition of Basal and Glucocorticoid-induced Insulin-like Growth Factor Binding Protein-1 and Phosphoenolpyruvate Carboxykinase Transcription. ROLES OF FORKHEAD AND INSULIN RESPONSE SEQUENCES J. Biol. Chem., August 31, 2001; 276(36): 33705 - 33710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Lechner, C. M. Croniger, P. Hakimi, C. Millward, C. Fekter, J. S. Yun, and R. W. Hanson The Use of Transgenic Mice to Analyze the Role of Accessory Factor Two in the Regulation of Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription during Diabetes J. Biol. Chem., June 15, 2001; 276(25): 22675 - 22679. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
