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Abstract:

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.

Registro:

Documento: Artículo
Título: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
Autor:Hoffmeister, A.; Ropolo, A.; Vasseur, S.; Mallo, G.V.; Bodeker, H.; Ritz-Laser, B.; Dressler, G.R.; Vaccaro, M.I.; Dagorn, J.-C.; Moreno, S.; Iovanna, J.L.
Filiación:Centre de Recherche INSERM, EMI 0116, Campus de Luminy, 163 avenue de Luminy, 13276 Marseille cedex 9, France
Departmento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121 Buenos Aires, Argentina
Diabetes Unit, Centre Médical Universitaire, 1211 Genève 4, Switzerland
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, United States
Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, 1428 Buenos Aires, Argentina
Centre de Recherche INSERM, EMI 116, Campus de Luminy, 163 avenue de Luminy, BP 172, 13009 Marseille, France
Palabras clave:Acetylation; Chemical activation; DNA; Proteins; Transcription factors; Biochemistry; DNA binding protein; glucagon; Pax2 transactivation domain interacting protein; protein p300; protein p8; recombinant protein; transcription factor; transcription factor Pax2A; transcription factor Pax2B; unclassified drug; acetylation; animal cell; article; controlled study; gene activation; gene control; gene targeting; genetic transfection; nonhuman; nucleotide sequence; priority journal; promoter region; protein expression; protein protein interaction; sequence homology; stress; transcription regulation; 3T3 Cells; Amino Acid Sequence; Animals; Basic Helix-Loop-Helix Transcription Factors; Carrier Proteins; COS Cells; DNA-Binding Proteins; E1A-Associated p300 Protein; Glucagon; Growth Substances; Hela Cells; Histidine; HMGA1a Protein; Humans; Mice; Models, Biological; Molecular Sequence Data; Neoplasm Proteins; Nuclear Proteins; PAX2 Transcription Factor; Precipitin Tests; Promoter Regions (Genetics); Protein Binding; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Trans-Activation (Genetics); Trans-Activators; Transcription Factors; Transfection; Animalia
Año:2002
Volumen:277
Número:25
Página de inicio:22314
Página de fin:22319
DOI: http://dx.doi.org/10.1074/jbc.M201657200
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:Basic Helix-Loop-Helix Transcription Factors; Carrier Proteins; DNA-Binding Proteins; E1A-Associated p300 Protein, EC 2.3.1.48; Ep300 protein, mouse; Glucagon, 9007-92-5; Growth Substances; Histidine, 71-00-1; HMGA1a Protein, 124544-67-8; Neoplasm Proteins; Nuclear Proteins; Nupr1 protein, mouse; P8 protein, human; PAX2 protein, human; Pax2 protein, mouse; PAX2 Transcription Factor; Paxip1 protein, mouse; PAXIP1L protein, human; Trans-Activators; Transcription Factors
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00219258_v277_n25_p22314_Hoffmeister.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v277_n25_p22314_Hoffmeister

Referencias:

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Citas:

---------- APA ----------
Hoffmeister, A., Ropolo, A., Vasseur, S., Mallo, G.V., Bodeker, H., Ritz-Laser, B., Dressler, G.R.,..., Iovanna, J.L. (2002) . 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. Journal of Biological Chemistry, 277(25), 22314-22319.
http://dx.doi.org/10.1074/jbc.M201657200
---------- CHICAGO ----------
Hoffmeister, A., Ropolo, A., Vasseur, S., Mallo, G.V., Bodeker, H., Ritz-Laser, B., et al. "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" . Journal of Biological Chemistry 277, no. 25 (2002) : 22314-22319.
http://dx.doi.org/10.1074/jbc.M201657200
---------- MLA ----------
Hoffmeister, A., Ropolo, A., Vasseur, S., Mallo, G.V., Bodeker, H., Ritz-Laser, B., et al. "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" . Journal of Biological Chemistry, vol. 277, no. 25, 2002, pp. 22314-22319.
http://dx.doi.org/10.1074/jbc.M201657200
---------- VANCOUVER ----------
Hoffmeister, A., Ropolo, A., Vasseur, S., Mallo, G.V., Bodeker, H., Ritz-Laser, B., et al. 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. J. Biol. Chem. 2002;277(25):22314-22319.
http://dx.doi.org/10.1074/jbc.M201657200