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

J. Biol. Chem., Vol. 277, Issue 25, 22314-22319, June 21, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/25/22314    most recent M201657200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hoffmeister, A. Articles by Iovanna, J. L. Search for Related Content PubMed PubMed Citation Articles by Hoffmeister, A. Articles by Iovanna, J. L.

The HMG-I/Y-related Protein p8 Binds to p300 and Pax2 trans-Activation Domain-interacting Protein to Regulate the trans-Activation Activity of the Pax2A and Pax2B Transcription Factors on the Glucagon Gene Promoter^*

Albrecht Hoffmeister^§, Alejandro Ropolo^¶§, Sophie Vasseur, Gustavo V. Mallo, Hans Bodeker, Beate Ritz-Laser, Gregory R. Dressler^**, Maria Ines Vaccaro^¶, Jean-Charles Dagorn, Silvia Moreno, and Juan Lucio Iovanna^§§

From the  Centre de Recherche INSERM, EMI 0116, 163 avenue de Luminy, Campus de Luminy, BP 172, 13276 Marseille cedex 9, France, the ^¶ Departmento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121 Buenos Aires, Argentina, the  Diabetes Unit, Centre Médical Universitaire, 1211 Genève 4, Switzerland, the ^** Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, and the  Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, 1428 Buenos Aires, Argentina

p8 is a nuclear DNA-binding protein, which was identified because its expression is strongly activated in response to several stresses. Biochemical and biophysical studies revealed that despite a weak sequence homology p8 is an HMG-I/Y-like protein, suggesting that p8 may be involved in transcription regulation. Results reported here strongly support this hypothesis. Using a pull-down approach, we found that p8 interacts with the general co-activator p300. We also found that, similar to the HMG proteins, p300 was able to acetylate recombinant p8 in vitro, although the significance of such modification remains to be determined. Then a screening by the two-hybrid system, using p8 as bait, allowed us to identify the Pax2 trans-activation domain-interacting protein (PTIP) as another partner of p8. Transient transfection studies revealed that PTIP is a strong inhibitor of the trans-activation activities of Pax2A and Pax2B on the glucagon gene promoter, which was chosen as a model because it is a target of the Pax2A and Pax2B transcription factors. This effect is completely abolished by co-transfection of p8 in glucagon-producing InRIG9 cells, indicating that p8 binding to PTIP prevents inhibition of the glucagon gene promoter. This was not observed in NIH3T3 fibroblasts that do not express glucagon. Finally, expression of p8 enhances the effect of p300 on Pax2A and Pax2B trans-activation of the glucagon gene promoter. These observations suggest that in glucagon-producing cells p8 is a positive cofactor of the activation of the glucagon gene promoter by Pax2A and Pax2B, both by recruiting the p300 cofactor to increase the Pax2A and Pax2B activities and by binding the Pax2-interacting protein PTIP to suppress its inhibition.

This article has been cited by other articles:

				T. M Clement, M. D Anway, M. Uzumcu, and M. K Skinner Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes Reproduction, September 1, 2007; 134(3): 455 - 472. [Abstract] [Full Text] [PDF]

				S. Goruppi, R. D. Patten, T. Force, and J. M. Kyriakis Helix-Loop-Helix Protein p8, a Transcriptional Regulator Required for Cardiomyocyte Hypertrophy and Cardiac Fibroblast Matrix Metalloprotease Induction Mol. Cell. Biol., February 1, 2007; 27(3): 993 - 1006. [Abstract] [Full Text] [PDF]

				C. Malicet, V. Giroux, S. Vasseur, J. C. Dagorn, J. L. Neira, and J. L. Iovanna Regulation of apoptosis by the p8/prothymosin {alpha} complex PNAS, February 21, 2006; 103(8): 2671 - 2676. [Abstract] [Full Text] [PDF]

				L. H. Kasper, T. Fukuyama, M. A. Biesen, F. Boussouar, C. Tong, A. de Pauw, P. J. Murray, J. M. A. van Deursen, and P. K. Brindle Conditional Knockout Mice Reveal Distinct Functions for the Global Transcriptional Coactivators CBP and p300 in T-Cell Development Mol. Cell. Biol., February 1, 2006; 26(3): 789 - 809. [Abstract] [Full Text] [PDF]

				H. Grasberger, U. Ringkananont, P. LeFrancois, M. Abramowicz, G. Vassart, and S. Refetoff Thyroid Transcription Factor 1 Rescues PAX8/p300 Synergism Impaired by a Natural PAX8 Paired Domain Mutation with Dominant Negative Activity Mol. Endocrinol., July 1, 2005; 19(7): 1779 - 1791. [Abstract] [Full Text] [PDF]

				G. Flock, X. Cao, and D. J. Drucker Pdx-1 Is Not Sufficient for Repression of Proglucagon Gene Transcription in Islet or Enteroendocrine Cells Endocrinology, January 1, 2005; 146(1): 441 - 449. [Abstract] [Full Text] [PDF]

				H. P. Mohammad, D. D. Seachrist, C. C. Quirk, and J. H. Nilson Reexpression of p8 Contributes to Tumorigenic Properties of Pituitary Cells and Appears in a Subset of Prolactinomas in Transgenic Mice that Hypersecrete Luteinizing Hormone Mol. Endocrinol., October 1, 2004; 18(10): 2583 - 2593. [Abstract] [Full Text] [PDF]

				S. Goruppi and J. M. Kyriakis The Pro-hypertrophic Basic Helix-Loop-Helix Protein p8 Is Degraded by the Ubiquitin/Proteasome System in a Protein Kinase B/Akt- and Glycogen Synthase Kinase-3-dependent Manner, whereas Endothelin Induction of p8 mRNA and Renal Mesangial Cell Hypertrophy Require NFAT4 J. Biol. Chem., May 14, 2004; 279(20): 20950 - 20958. [Abstract] [Full Text] [PDF]

				S. Vasseur, E. Folch-Puy, V. Hlouschek, S. Garcia, F. Fiedler, M. M. Lerch, J. C. Dagorn, D. Closa, and J. L. Iovanna p8 Improves Pancreatic Response to Acute Pancreatitis by Enhancing the Expression of the Anti-inflammatory Protein Pancreatitis-associated Protein I J. Biol. Chem., February 20, 2004; 279(8): 7199 - 7207. [Abstract] [Full Text] [PDF]

				E. A. Cho, M. J. Prindle, and G. R. Dressler BRCT Domain-Containing Protein PTIP Is Essential for Progression through Mitosis Mol. Cell. Biol., March 1, 2003; 23(5): 1666 - 1673. [Abstract] [Full Text] [PDF]

				C. C. Quirk, D. D. Seachrist, and J. H. Nilson Embryonic Expression of the Luteinizing Hormone beta Gene Appears to Be Coupled to the Transient Appearance of p8, a High Mobility Group-related Transcription Factor J. Biol. Chem., January 10, 2003; 278(3): 1680 - 1685. [Abstract] [Full Text] [PDF]

				G. Flock and D. J. Drucker Pax-2 Activates the Proglucagon Gene Promoter But Is Not Essential for Proglucagon Gene Expression or Development of Proglucagon-Producing Cell Lineages in the Murine Pancreas or Intestine Mol. Endocrinol., October 1, 2002; 16(10): 2349 - 2359. [Abstract] [Full Text] [PDF]