This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tessari, M. A.
Right arrow Articles by Manfioletti, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tessari, M. A.
Right arrow Articles by Manfioletti, G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2003, p. 9104-9116, Vol. 23, No. 24
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.24.9104-9116.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Transcriptional Activation of the Cyclin A Gene by the Architectural Transcription Factor HMGA2

Michela A. Tessari,1 Monica Gostissa,2 Sandro Altamura,1 Riccardo Sgarra,1 Alessandra Rustighi,3 Clio Salvagno,1,2 Giuseppina Caretti,4 Carol Imbriano,4 Roberto Mantovani,4,{dagger} Giannino Del Sal,1,2,5 Vincenzo Giancotti,3 and Guidalberto Manfioletti1*

Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole,1 Centre of Excellence in Biocristallography, University of Trieste, 34127 Trieste,5 Laboratorio Nazionale, Consorzio Interuniversitario Biotecnologie, AREA Science Park, 34012 Trieste,2 Dipartimento di Patologia e Medicina Sperimentale e Clinica, University of Udine, 33100 Udine,3 Dipartimento di Biologia Animale, University of Modena e Reggio Emilia, 41100 Modena, Italy4

Received 5 June 2003/ Returned for modification 15 July 2003/ Accepted 19 September 2003

The HMGA2 protein belongs to the HMGA family of architectural transcription factors, which play an important role in chromatin organization. HMGA proteins are overexpressed in several experimental and human tumors and have been implicated in the process of neoplastic transformation. Hmga2 knockout results in the pygmy phenotype in mice and in a decreased growth rate of embryonic fibroblasts, thus indicating a role for HMGA2 in cell proliferation. Here we show that HMGA2 associates with the E1A-regulated transcriptional repressor p120E4F, interfering with p120E4F binding to the cyclin A promoter. Ectopic expression of HMGA2 results in the activation of the cyclin A promoter and induction of the endogenous cyclin A gene. In addition, chromatin immunoprecipitation experiments show that HMGA2 associates with the cyclin A promoter only when the gene is transcriptionally activated. These data identify the cyclin A gene as a cellular target for HMGA2 and, for the first time, suggest a mechanism for HMGA2-dependent cell cycle regulation.

* Corresponding author. Mailing address: Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, University of Trieste, via L. Giorgieri 1, 34127 Trieste, Italy. Phone: 39 040 5583675. Fax: 39 040 5583694. E-mail: manfiole{at}univ.trieste.it.

{dagger} Present address: Dipartimento di Genetica e di Biologia dei Microrganismi, University of Milan, 20133 Milan, Italy.

Molecular and Cellular Biology, December 2003, p. 9104-9116, Vol. 23, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.24.9104-9116.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Watanabe, S., Ueda, Y., Akaboshi, S.-i., Hino, Y., Sekita, Y., Nakao, M. (2009). HMGA2 Maintains Oncogenic RAS-Induced Epithelial-Mesenchymal Transition in Human Pancreatic Cancer Cells. Am. J. Pathol. 174: 854-868 [Abstract] [Full Text]  
  • Farras, R., Baldin, V., Gallach, S., Acquaviva, C., Bossis, G., Jariel-Encontre, I., Piechaczyk, M. (2008). JunB Breakdown in Mid-/Late G2 Is Required for Down-Regulation of Cyclin A2 Levels and Proper Mitosis. Mol. Cell. Biol. 28: 4173-4187 [Abstract] [Full Text]  
  • Cao, X., Clavijo, C., Li, X., Lin, H. H., Chen, Y., Shih, H.-M., Ann, D. K. (2008). SUMOylation of HMGA2: selective destabilization of promyelocytic leukemia protein via proteasome. Molecular Cancer Therapeutics 7: 923-934 [Abstract] [Full Text]  
  • Cleynen, I., Brants, J. R., Peeters, K., Deckers, R., Debiec-Rychter, M., Sciot, R., Van de Ven, W. J.M., Petit, M. M.R. (2007). HMGA2 Regulates Transcription of the Imp2 Gene via an Intronic Regulatory Element in Cooperation with Nuclear Factor-{kappa}B. Mol Cancer Res 5: 363-372 [Abstract] [Full Text]  
  • Cattaruzzi, G., Altamura, S., Tessari, M. A., Rustighi, A., Giancotti, V., Pucillo, C., Manfioletti, G. (2007). The second AT-hook of the architectural transcription factor HMGA2 is determinant for nuclear localization and function. Nucleic Acids Res 35: 1751-1760 [Abstract] [Full Text]  
  • Inoue, N., Izui-Sarumaru, T., Murakami, Y., Endo, Y., Nishimura, J.-I., Kurokawa, K., Kuwayama, M., Shime, H., Machii, T., Kanakura, Y., Meyers, G., Wittwer, C., Chen, Z., Babcock, W., Frei-Lahr, D., Parker, C. J., Kinoshita, T. (2006). Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH). Blood 108: 4232-4236 [Abstract] [Full Text]  
  • Shlapobersky, M., Sanders, R., Clark, C., Spector, D. H. (2006). Repression of HMGA2 Gene Expression by Human Cytomegalovirus Involves the IE2 86-Kilodalton Protein and Is Necessary for Efficient Viral Replication and Inhibition of Cyclin A Transcription.. J. Virol. 80: 9951-9961 [Abstract] [Full Text]  
  • Zaidi, M. R., Okada, Y., Chada, K. K. (2006). Misexpression of Full-length HMGA2 Induces Benign Mesenchymal Tumors in Mice.. Cancer Res. 66: 7453-7459 [Abstract] [Full Text]  
  • Chagraoui, J., Niessen, S. L., Lessard, J., Girard, S., Coulombe, P., Sauvageau, M., Meloche, S., Sauvageau, G. (2006). E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells. Genes Dev. 20: 2110-2120 [Abstract] [Full Text]  
  • Matsui, Y, Hasegawa, T, Kubo, T, Goto, T, Yukata, K, Endo, K, Bando, Y, Yasui, N (2006). Intrapatellar tendon lipoma with chondro-osseous differentiation: detection of HMGA2-LPP fusion gene transcript.. J. Clin. Pathol. 59: 434-436 [Abstract] [Full Text]  
  • Frasca, F., Rustighi, A., Malaguarnera, R., Altamura, S., Vigneri, P., Del Sal, G., Giancotti, V., Pezzino, V., Vigneri, R., Manfioletti, G. (2006). HMGA1 Inhibits the Function of p53 Family Members in Thyroid Cancer Cells.. Cancer Res. 66: 2980-2989 [Abstract] [Full Text]  
  • Sgarra, R., Lee, J., Tessari, M. A., Altamura, S., Spolaore, B., Giancotti, V., Bedford, M. T., Manfioletti, G. (2006). The AT-hook of the Chromatin Architectural Transcription Factor High Mobility Group A1a Is Arginine-methylated by Protein Arginine Methyltransferase 6. J. Biol. Chem. 281: 3764-3772 [Abstract] [Full Text]  
  • Boo, L. M., Lin, H. H., Chung, V., Zhou, B., Louie, S. G., O'Reilly, M. A., Yen, Y., Ann, D. K. (2005). High Mobility Group A2 Potentiates Genotoxic Stress in Part through the Modulation of Basal and DNA Damage-Dependent Phosphatidylinositol 3-Kinase-Related Protein Kinase Activation. Cancer Res. 65: 6622-6630 [Abstract] [Full Text]  
  • Furuta, S., Jiang, X., Gu, B., Cheng, E., Chen, P.-L., Lee, W.-H. (2005). Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary epithelial cells. Proc. Natl. Acad. Sci. USA 102: 9176-9181 [Abstract] [Full Text]  
  • Ahmed-Choudhury, J., Agathanggelou, A., Fenton, S. L., Ricketts, C., Clark, G. J., Maher, E. R., Latif, F. (2005). Transcriptional Regulation of Cyclin A2 by RASSF1A through the Enhanced Binding of p120E4F to the Cyclin A2 Promoter. Cancer Res. 65: 2690-2697 [Abstract] [Full Text]  
  • Crombez, K. R.M.O., Vanoirbeek, E. M.R., Van de Ven, W. J.M., Petit, M. M.R. (2005). Transactivation Functions of the Tumor-Specific HMGA2/LPP Fusion Protein Are Augmented by Wild-Type HMGA2. Mol Cancer Res 3: 63-70 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»