HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 26, 23360-23368, June 27, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/26/23360    most recent M300771200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ragione, F. D. Articles by Zappia, V. Search for Related Content PubMed PubMed Citation Articles by Ragione, F. D. Articles by Zappia, V. Social Bookmarking                      What's this?

p21^Cip1 Gene Expression Is Modulated by Egr1

A NOVEL REGULATORY MECHANISM INVOLVED IN THE RESVERATROL ANTIPROLIFERATIVE EFFECT^*

Fulvio Della Ragione , Valeria Cucciolla, Vittoria Criniti, Stefania Indaco, Adriana Borriello and Vincenzo Zappia

From the Department of Biochemistry and Biophysics "F. Cedrangolo," Second University of Naples, 80138, Naples, Italy

Epidemiological observations indicate that resveratrol, a natural antioxidant stilbene, exerts cardioprotective and chemopreventive effects. Moreover, the molecule induces in vitro cell growth inhibition and differentiation. Using human erythroleukemic K562 cells as model system, we demonstrated that resveratrol induces a remarkable -globin synthesis, the erythroid differentiation being linked to impairment of cell proliferation, increased p21^Cip1 expression and inhibition of cdk2 activity. The up-regulation of p21^Cip1 transcription is prevented by cycloheximide, indicating the requirement of intermediate protein(s), which, in turn, regulate gene expression. The quantitative analysis of some transcription factors involved in the erythroid lineage, namely GATA-1, GATA-2, and Egr1, indicated that resveratrol selectively up-regulates Egr1 by an Erk1/2-dependent mechanism. The presence of an Egr1 consensus sequence in the p21^Cip1 promoter suggested the hypothesis that this transcription factor directly regulates the expression of the cdk inhibitor. Transfection studies with deleted gene promoter constructs, as well as EMSA, pull-down, and chromatin immunoprecipitation experiments substantiated this view, demonstrating that Egr1 binds in vitro and in vivo to the identified consensus sequence of the p21^Cip1 promoter. Moreover, an Egr1 phosphorothioate antisense hinders p21^Cip1 accumulation and the antiproliferative effects of resveratrol. In conclusion, this is the first demonstration that Egr1 controls p21^Cip1 expression by directly interacting with a specific sequence on its gene promoter. The identified regulatory mechanism also contributes to the clarification of the complex chemopreventive and antiproliferative properties of resveratrol.

Received for publication, January 23, 2003 , and in revised form, April 9, 2003.

^* This work was supported in part by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC) and from MURST (Progetti di Rilevante Interesse Nazionale). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Biochemistry and Biophysics F. Cedrangolo, Second University of Naples, Via Costantinopoli, 16, 80138, Naples, Italy. Tel.: 39-081-5665812; Fax: 39-081-441688; E-mail: fulvio.dellaragione{at}unina2.it.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Manea, S. A. Manea, A. V. Gafencu, M. Raicu, and M. Simionescu AP-1-Dependent Transcriptional Regulation of NADPH Oxidase in Human Aortic Smooth Muscle Cells: Role of p22phox Subunit Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 878 - 885. [Abstract] [Full Text] [PDF]

				B. H. Choi, C. G. Kim, Y.-S. Bae, Y. Lim, Y. H. Lee, and S. Y. Shin p21Waf1/Cip1 Expression by Curcumin in U-87MG Human Glioma Cells: Role of Early Growth Response-1 Expression Cancer Res., March 1, 2008; 68(5): 1369 - 1377. [Abstract] [Full Text] [PDF]

				V. Cucciolla, A. Borriello, M. Criscuolo, A. A. Sinisi, D. Bencivenga, A. Tramontano, A. C. Scudieri, A. Oliva, V. Zappia, and F. D. Ragione Histone deacetylase inhibitors upregulate p57Kip2 level by enhancing its expression through Sp1 transcription factor Carcinogenesis, March 1, 2008; 29(3): 560 - 567. [Abstract] [Full Text] [PDF]

				P. Blancafort, M. P. Tschan, S. Bergquist, D. Guthy, A. Brachat, D. A. Sheeter, B. E. Torbett, D. Erdmann, and C. F. Barbas III Modulation of drug resistance by artificial transcription factors Mol. Cancer Ther., March 1, 2008; 7(3): 688 - 697. [Abstract] [Full Text] [PDF]

				X. Hou, E. W. Arvisais, C. Jiang, D.-b. Chen, S. K. Roy, J. L. Pate, T. R. Hansen, B. R. Rueda, and J. S. Davis Prostaglandin F2{alpha} Stimulates the Expression and Secretion of Transforming Growth Factor B1 Via Induction of the Early Growth Response 1 Gene (EGR1) in the Bovine Corpus Luteum Mol. Endocrinol., February 1, 2008; 22(2): 403 - 414. [Abstract] [Full Text] [PDF]

				M. Mohan, P. P. Aye, J. T. Borda, X. Alvarez, and A. A. Lackner Gastrointestinal Disease in Simian Immunodeficiency Virus-Infected Rhesus Macaques Is Characterized by Proinflammatory Dysregulation of the Interleukin-6-Janus Kinase/Signal Transducer and Activator of Transcription3 Pathway Am. J. Pathol., December 1, 2007; 171(6): 1952 - 1965. [Abstract] [Full Text] [PDF]

				M. H. Ko and L. Puglielli The Sterol Carrier Protein SCP-x/Pro-SCP-2 Gene Has Transcriptional Activity and Regulates the Alzheimer Disease {gamma}-Secretase J. Biol. Chem., July 6, 2007; 282(27): 19742 - 19752. [Abstract] [Full Text] [PDF]

				C. P. Fanton, M. W. Rowe, E. J. Moler, M. Ison-Dugenny, S. K. De Long, K. Rendahl, Y. Shao, T. Slabiak, T. G. Gesner, and M. L. MacKichan Development of a Screening Assay for Surrogate Markers of Chk1 Inhibitor-Induced Cell Cycle Release J Biomol Screen, October 1, 2006; 11(7): 792 - 806. [Abstract] [PDF]

				S. Perrotta, A. Borriello, A. Scaloni, L. De Franceschi, A. M. Brunati, F. Turrini, V. Nigro, E. Miraglia del Giudice, B. Nobili, M. L. Conte, et al. The N-terminal 11 amino acids of human erythrocyte band 3 are critical for aldolase binding and protein phosphorylation: implications for band 3 function Blood, December 15, 2005; 106(13): 4359 - 4366. [Abstract] [Full Text] [PDF]

				P. Galletti, C. I. Di Gennaro, V. Migliardi, S. Indaco, F. Della Ragione, C. Manna, P. Chiodini, G. Capasso, and V. Zappia Diverse effects of natural antioxidants on cyclosporin cytotoxicity in rat renal tubular cells Nephrol. Dial. Transplant., August 1, 2005; 20(8): 1551 - 1558. [Abstract] [Full Text] [PDF]

				A. Slack, Z. Chen, R. Tonelli, M. Pule, L. Hunt, A. Pession, and J. M. Shohet The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma PNAS, January 18, 2005; 102(3): 731 - 736. [Abstract] [Full Text] [PDF]

				V. Krishnan and S. L. Zeichner Host Cell Gene Expression during Human Immunodeficiency Virus Type 1 Latency and Reactivation and Effects of Targeting Genes That Are Differentially Expressed in Viral Latency J. Virol., September 1, 2004; 78(17): 9458 - 9473. [Abstract] [Full Text] [PDF]

				M. M. Monick, K. Cameron, L. S. Powers, N. S. Butler, D. McCoy, R. K. Mallampalli, and G. W. Hunninghake Sphingosine Kinase Mediates Activation of Extracellular Signal-Related Kinase and Akt by Respiratory Syncytial Virus Am. J. Respir. Cell Mol. Biol., June 1, 2004; 30(6): 844 - 852. [Abstract] [Full Text] [PDF]

				K. Subbaramaiah, K. Yoshimatsu, E. Scherl, K. M. Das, K. D. Glazier, D. Golijanin, R. A. Soslow, T. Tanabe, H. Naraba, and A. J. Dannenberg Microsomal Prostaglandin E Synthase-1 Is Overexpressed in Inflammatory Bowel Disease: EVIDENCE FOR INVOLVEMENT OF THE TRANSCRIPTION FACTOR Egr-1 J. Biol. Chem., March 26, 2004; 279(13): 12647 - 12658. [Abstract] [Full Text] [PDF]