PIAS gamma represses the transcriptional activation induced by the nuclear receptor Nurr1

Galleguillos D; Vecchiola, A; Fuentealba, JA; Ojeda V.; Alvarez, K; Gomez A.; Andres, ME

Abstract

Nurr1 is a transcription factor essential for the development of ventral dopaminergic neurons. In search for regulatory mechanisms of Nurr1 function, we identified the SUMO (small ubiquitin-like modifier)-E3 ubiquitin-protein isopeptide ligase, PIAS?, as an interaction partner of Nurr1. Overexpressed PIAS? and Nurr1 co-localize in the nuclei of transfected cells, and their interaction is demonstrated through co-immunoprecipitation and glutathione S-transferase pulldown assays. Co-expression of PIAS? with Nurr1 results in a potent repression of Nurr1-dependent transcriptional activation of an artificial NGFI-B response element (NBRE) reporter as well as of a reporter driven by the native tyrosine hydroxylase promoter. We identified two consensus sumoylation sites in Nurr1. The substitution of lysine 91 by arginine in one SUMO site enhanced the transcriptional activity of Nurr1, whereas the substitution of lysine 577 by arginine in the second SUMO site decreased transcriptional activity of Nurr1. Interestingly, PIAS?-induced repression of Nurr1 activity does not require the two sumoylation sites, because each mutant is repressed as efficiently as the wild type Nurr1. In addition, the mutations do not alter Nurr1 nuclear localization. Finally, we provide evidence that Nurr1 and PIAS? co-exist in several nuclei of the rodent central nervous system by demonstrating the co-expression of Nurr1 protein and PIAS? mRNA in the same cells. In conclusion, our studies identified PIAS? as a transcriptional co-regulator of Nurr1 and suggest that this interaction may have a physiological role in regulating the expression of Nurr1 target genes.

Más información

Título según WOS: PIAS gamma represses the transcriptional activation induced by the nuclear receptor Nurr1
Título según SCOPUS: PIAS? Represses the Transcriptional Activation Induced by the Nuclear Receptor Nurr1
Título de la Revista: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 279
Número: 3
Editorial: Elsevier
Fecha de publicación: 2004
Página de inicio: 2005
Página final: 2011
Idioma: English
URL: http://www.jbc.org/cgi/doi/10.1074/jbc.M308113200
DOI:

10.1074/jbc.M308113200

Notas: ISI, SCOPUS