Sp1 is a ubiquitous nuclear factor that plays a key role in maintaining basal transcription of 'house-keeping' genes. However, recent evidence points to a more important function for Sp1 in mediating 'cross-talk' between selected signaling cascades to regulate the target genes that respond to these pathways. The role of Sp1 in mediating the actions of the peptide hormone insulin is of specific interest and serves as a model for detailing effects of intracellular signaling on Sp1 activity. This review summarizes studies suggesting that changes in Sp1 phosphorylation provide one potential mechanism for manipulating activity of this protein. A growing body of evidence reveals that the DNA binding and transcription activity of Sp1 may increase or decrease in response to changes in phosphorylation. This enables 'fine-tuning' of Sp1 activity for regulation of gene transcription. Several mechanisms exist by which Sp1 alters gene activity in response to insulin. These include independent Sp1 activity as well as collaboration or competition with others factors. This review points to an ever-increasing role for Sp1 in regulating the transcription of genes in response to extracellular signals such as insulin.

This article has been cited by other articles:

				H. Teng, R. D. Ballim, S. Mowla, and S. Prince Phosphorylation of Histone H3 by Protein Kinase C Signaling Plays a Critical Role in the Regulation of the Developmentally Important TBX2 Gene J. Biol. Chem., September 25, 2009; 284(39): 26368 - 26376. [Abstract] [Full Text] [PDF]

				X. Du, R. L. Rosenfield, and K. Qin KLF15 Is a Transcriptional Regulator of the Human 17{beta}-Hydroxysteroid Dehydrogenase Type 5 Gene. A Potential Link between Regulation of Testosterone Production and Fat Stores in Women J. Clin. Endocrinol. Metab., July 1, 2009; 94(7): 2594 - 2601. [Abstract] [Full Text] [PDF]

				Y. S. Devi, A. Shehu, C. Stocco, J. Halperin, J. Le, A. M. Seibold, M. Lahav, N. Binart, and G. Gibori Regulation of Transcription Factors and Repression of Sp1 by Prolactin Signaling Through the Short Isoform of Its Cognate Receptor Endocrinology, July 1, 2009; 150(7): 3327 - 3335. [Abstract] [Full Text] [PDF]

				S. Wei, H.-C. Chuang, W.-C. Tsai, H.-C. Yang, S.-R. Ho, A. J. Paterson, S. K. Kulp, and C.-S. Chen Thiazolidinediones Mimic Glucose Starvation in Facilitating Sp1 Degradation through the Up-Regulation of {beta}-Transducin Repeat-Containing Protein Mol. Pharmacol., July 1, 2009; 76(1): 47 - 57. [Abstract] [Full Text] [PDF]

				J. A. Willoughby Sr., S. N. Sundar, M. Cheung, A. S. Tin, J. Modiano, and G. L. Firestone Artemisinin Blocks Prostate Cancer Growth and Cell Cycle Progression by Disrupting Sp1 Interactions with the Cyclin-dependent Kinase-4 (CDK4) Promoter and Inhibiting CDK4 Gene Expression J. Biol. Chem., January 23, 2009; 284(4): 2203 - 2213. [Abstract] [Full Text] [PDF]

				J. Chahal, C.-C. Chen, M. J. Rane, J. P. Moore, M. T. Barati, Y. Song, and B. C. Villafuerte Regulation of Insulin-Response Element Binding Protein-1 in Obesity and Diabetes: Potential Role in Impaired Insulin-Induced Gene Transcription Endocrinology, October 1, 2008; 149(10): 4829 - 4836. [Abstract] [Full Text] [PDF]

				Y. Quan, Z.-L. Ji, X. Wang, A. M. Tartakoff, and T. Tao Evolutionary and Transcriptional Analysis of Karyopherin {beta} Superfamily Proteins Mol. Cell. Proteomics, July 1, 2008; 7(7): 1254 - 1269. [Abstract] [Full Text] [PDF]

				X. Luo, J. Xiao, H. Lin, Y. Lu, B. Yang, and Z. Wang Genomic structure, transcriptional control, and tissue distribution of HERG1 and KCNQ1 genes Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1371 - H1380. [Abstract] [Full Text] [PDF]

				T. P. Ellen, Q. Ke, P. Zhang, and M. Costa NDRG1, a growth and cancer related gene: regulation of gene expression and function in normal and disease states Carcinogenesis, January 1, 2008; 29(1): 2 - 8. [Abstract] [Full Text] [PDF]

				K. Murao, X. Yu, H. Imachi, W. M. Cao, K. Chen, K. Matsumoto, T. Nishiuchi, N. C. W. Wong, and T. Ishida Hyperglycemia suppresses hepatic scavenger receptor class B type I expression Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E78 - E87. [Abstract] [Full Text] [PDF]

				D. Y. C. Wu, R. Wu, Y. Chen, N. Tarasova, and M. M. J. Chang PMA Stimulates MUC5B Gene Expression through an Sp1-Based Mechanism in Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., November 1, 2007; 37(5): 589 - 597. [Abstract] [Full Text] [PDF]

				X. Deng, C. Yellaturu, L. Cagen, H. G. Wilcox, E. A. Park, R. Raghow, and M. B. Elam Expression of the Rat Sterol Regulatory Element-binding Protein-1c Gene in Response to Insulin Is Mediated by Increased Transactivating Capacity of Specificity Protein 1 (Sp1) J. Biol. Chem., June 15, 2007; 282(24): 17517 - 17529. [Abstract] [Full Text] [PDF]

				M J Moreno-Aliaga, M M Swarbrick, S Lorente-Cebrian, K L Stanhope, P J Havel, and J A Martinez Sp1-mediated transcription is involved in the induction of leptin by insulin-stimulated glucose metabolism J. Mol. Endocrinol., May 1, 2007; 38(5): 537 - 546. [Abstract] [Full Text] [PDF]

				M Egea, I Meton, and I V Baanante Sp1 and Sp3 regulate glucokinase gene transcription in the liver of gilthead sea bream (Sparus aurata) J. Mol. Endocrinol., April 1, 2007; 38(4): 481 - 492. [Abstract] [Full Text] [PDF]

				A. C. Marinovic, B. Zheng, W. E. Mitch, and S. R. Price Tissue-specific regulation of ubiquitin (UbC) transcription by glucocorticoids: in vivo and in vitro analyses Am J Physiol Renal Physiol, February 1, 2007; 292(2): F660 - F666. [Abstract] [Full Text] [PDF]

				Y. Zhang, M. Liao, and M. L. Dufau Phosphatidylinositol 3-Kinase/Protein Kinase C{zeta}-Induced Phosphorylation of Sp1 and p107 Repressor Release Have a Critical Role in Histone Deacetylase Inhibitor-Mediated Depression of Transcription of the Luteinizing Hormone Receptor Gene Mol. Cell. Biol., September 15, 2006; 26(18): 6748 - 6761. [Abstract] [Full Text] [PDF]

				L. Barre, N. Venkatesan, J. Magdalou, P. Netter, S. Fournel-Gigleux, and M. Ouzzine Evidence of calcium-dependent pathway in the regulation of human {beta}1,3-glucuronosyltransferase-1 (GlcAT-I) gene expression: a key enzyme in proteoglycan synthesis FASEB J, August 1, 2006; 20(10): 1692 - 1694. [Abstract] [Full Text] [PDF]

				K. Hasegawa, S. Wakino, T. Tanaka, M. Kimoto, S. Tatematsu, T. Kanda, K. Yoshioka, K. Homma, N. Sugano, M. Kurabayashi, et al. Dimethylarginine Dimethylaminohydrolase 2 Increases Vascular Endothelial Growth Factor Expression Through Sp1 Transcription Factor in Endothelial Cells Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1488 - 1494. [Abstract] [Full Text] [PDF]

				C. Menzaghi, G. Paroni, C. De Bonis, T. Soccio, A. Marucci, S. Bacci, and V. Trischitta The -318 C>G Single-Nucleotide Polymorphism in GNAI2 Gene Promoter Region Impairs Transcriptional Activity through Specific Binding of Sp1 Transcription Factor and Is Associated with High Blood Pressure in Caucasians from Italy. J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S115 - S119. [Abstract] [Full Text] [PDF]

				R. Furbass, A. Winter, R. Fries, and C. Kuhn Alleles of the bovine DGAT1 variable number of tandem repeat associated with a milk fat QTL at chromosome 14 can stimulate gene expression. Physiol Genomics, March 13, 2006; 25(1): 116 - 120. [Abstract] [Full Text] [PDF]

				G. Majumdar, A. Harrington, J. Hungerford, A. Martinez-Hernandez, I. C. Gerling, R. Raghow, and S. Solomon Insulin Dynamically Regulates Calmodulin Gene Expression by Sequential O-Glycosylation and Phosphorylation of Sp1 and Its Subcellular Compartmentalization in Liver Cells J. Biol. Chem., February 10, 2006; 281(6): 3642 - 3650. [Abstract] [Full Text] [PDF]

				A. D. Mooradian, M. J. Haas, and N. C. W. Wong The Effect of Select Nutrients on Serum High-Density Lipoprotein Cholesterol and Apolipoprotein A-I Levels Endocr. Rev., February 1, 2006; 27(1): 2 - 16. [Abstract] [Full Text] [PDF]

				K. Qin, D. A. Ehrmann, N. Cox, S. Refetoff, and R. L. Rosenfield Identification of a Functional Polymorphism of the Human Type 5 17{beta}-Hydroxysteroid Dehydrogenase Gene Associated with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 270 - 276. [Abstract] [Full Text] [PDF]

				T. Hashimoto, T. Nakamura, H. Maegawa, Y. Nishio, K. Egawa, and A. Kashiwagi Regulation of ATP-sensitive Potassium Channel Subunit Kir6.2 Expression in Rat Intestinal Insulin-producing Progenitor Cells J. Biol. Chem., January 21, 2005; 280(3): 1893 - 1900. [Abstract] [Full Text] [PDF]

				S. K. Das, W. Chu, Z. Zhang, S. J. Hasstedt, and S. C. Elbein Calsquestrin 1 (CASQ1) Gene Polymorphisms Under Chromosome 1q21 Linkage Peak Are Associated With Type 2 Diabetes in Northern European Caucasians Diabetes, December 1, 2004; 53(12): 3300 - 3306. [Abstract] [Full Text] [PDF]

				Y. Ng, I. Tan, L. Lim, and T. Leung Expression of the Human Myotonic Dystrophy Kinase-related Cdc42-binding Kinase {gamma} Is Regulated by Promoter DNA Methylation and Sp1 Binding J. Biol. Chem., August 13, 2004; 279(33): 34156 - 34164. [Abstract] [Full Text] [PDF]

				A. Rajakumar, S. Thamotharan, N. Raychaudhuri, R. K. Menon, and S. U. Devaskar Trans-activators Regulating Neuronal Glucose Transporter Isoform-3 Gene Expression in Mammalian Neurons J. Biol. Chem., June 18, 2004; 279(25): 26768 - 26779. [Abstract] [Full Text] [PDF]

				D. Wei, L. Wang, Y. He, H. Q. Xiong, J. L. Abbruzzese, and K. Xie Celecoxib Inhibits Vascular Endothelial Growth Factor Expression in and Reduces Angiogenesis and Metastasis of Human Pancreatic Cancer via Suppression of Sp1 Transcription Factor Activity Cancer Res., March 15, 2004; 64(6): 2030 - 2038. [Abstract] [Full Text] [PDF]

				A. D. Mooradian, M. J. Haas, and N. C.W. Wong Transcriptional Control of Apolipoprotein A-I Gene Expression in Diabetes Diabetes, March 1, 2004; 53(3): 513 - 520. [Abstract] [Full Text] [PDF]

				M. R. Bonello and L. M. Khachigian Fibroblast Growth Factor-2 Represses Platelet-derived Growth Factor Receptor-{alpha} (PDGFR-{alpha}) Transcription via ERK1/2-dependent Sp1 Phosphorylation and an Atypical cis-Acting Element in the Proximal PDGFR-{alpha} Promoter J. Biol. Chem., January 23, 2004; 279(4): 2377 - 2382. [Abstract] [Full Text] [PDF]

				H. Higuchi, A. Grambihler, A. Canbay, S. F. Bronk, and G. J. Gores Bile Acids Up-regulate Death Receptor 5/TRAIL-receptor 2 Expression via a c-Jun N-terminal Kinase-dependent Pathway Involving Sp1 J. Biol. Chem., January 2, 2004; 279(1): 51 - 60. [Abstract] [Full Text] [PDF]

				S. Shimizu, S. Ugi, H. Maegawa, K. Egawa, Y. Nishio, T. Yoshizaki, K. Shi, Y. Nagai, K. Morino, K.-i. Nemoto, et al. Protein-tyrosine Phosphatase 1B as New Activator for Hepatic Lipogenesis via Sterol Regulatory Element-binding Protein-1 Gene Expression J. Biol. Chem., October 31, 2003; 278(44): 43095 - 43101. [Abstract] [Full Text] [PDF]

				G. Tiwari, H. Sakaue, J. R. Pollack, and R. A. Roth Gene Expression Profiling in Prostate Cancer Cells With Akt Activation Reveals Fra-1 As an Akt-Inducible Gene Mol. Cancer Res., April 1, 2003; 1(6): 475 - 484. [Abstract] [Full Text] [PDF]