Modification of the transcription factor Pax8 by SUMO (Abstract/Poster in atti di convegno)

Type
Label
  • Modification of the transcription factor Pax8 by SUMO (Abstract/Poster in atti di convegno) (literal)
Anno
  • 2006-01-01T00:00:00+01:00 (literal)
Alternative label
  • de Cristofaro T, Pappalardo A, Mascia A, Zannini S (2006)
    Modification of the transcription factor Pax8 by SUMO
    in 31st Annual Meeting of the European Thyroid Association, Napoli
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • de Cristofaro T, Pappalardo A, Mascia A, Zannini S (literal)
Pagina inizio
  • 168 (literal)
Pagina fine
  • 168 (literal)
Note
  • Abstract (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Istituto di Endocrinologia e Oncologia Sperimentale 'G. Salvatore'-CNR; Dpt. Biologia e Patologia Cellulare e Molecolare, Universita' di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italy (literal)
Titolo
  • Modification of the transcription factor Pax8 by SUMO (literal)
Abstract
  • The transcription factor Pax8 is involved in the expression of the thyroid-specific genes that are considered markers of the differentiated phenotype. The regulation of Pax8 activity is likely to play a key role in thyroid differentiation as well as in thyroid malignant transformation. We focused our attention on the study of Pax8 post-translational modification such as sumoylation. The analysis of Pax8 protein sequence revealed the presence of one sumoylation consensus motif (YKXE), strongly conserved among mammals, amphibians and fish. Sumoylation is a dynamic and reversible process that regulates (positively or negatively) gene expression by altering transcription factor stability, protein-protein interactions and subcellular localization. At present, there are three SUMO isoforms (SUMO-1, SUMO-2 and SUMO-3) that may play distinguishable roles in the control of the activity of target proteins. We have demonstrated that Pax8 is indeed sumoylated by the addition of a single SUMO molecule by all SUMO isoforms. Moreover, we have generated a substitution mutant in which the candidate lysine (K309) was replaced with an arginine by site-directed mutagenesis, and we have determined that such mutant is no longer modified by SUMO. In addition, we have analyzed whether members of the PIAS family of proteins (protein inhibitor of activated STAT) could function as SUMO ligases and we have demonstrated that PIAS1 and PIASy are able to increase the fraction of sumoylated Pax8. Our goal was then to identify a functional role for Pax8 sumoylation. Therefore, by transient transfection assays in HeLa cells and in thyroid PC Cl3 cells we have analyzed whether sumoylation affects the ability of Pax8 to activate transcription from the thyroid-specific gene promoters such as thyroglobulin, thyroperoxidase and NIS. At the same time, we have also investigated whether sumoylation modifies Pax8 subcellular localization and protein stability. Such experiments are ongoing and results will be presented. (literal)
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