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Sumoylation of the net inhibitory domain (NID) is stimulated by PIAS1 and has a negative effect on the transcriptional activity of Net

Abstract

Net (Elk-3, Sap-2, Erp) and the related ternary complex factors Elk-1 and Sap-1 are effectors of multiple signalling pathways at the transcriptional level and play a key role in the dynamic regulation of gene expression. Net is distinct from Elk-1 and Sap-1, in that it is a strong repressor of transcription that is converted to an activator by the Ras/Erk signalling pathway. Two autonomous repression domains of Net, the NID and the CID, mediate repression. We have previously shown that the co-repressor CtBP is implicated in repression by the CID. In this report we show that repression by the NID involves a different pathway, sumoylation by Ubc9 and PIAS1. PIAS1 interacts with the NID in the two-hybrid assay and in vitro. Ubc9 and PIAS1 stimulate sumoylation in vivo of lysine 162 in the NID. Sumoylation of lysine 162 increases repression by Net and decreases the positive activity of Net. These results increase our understanding of how one of the ternary complex factors regulates transcription, and contribute to the understanding of how different domains of a transcription factor participate in the complexity of regulation of gene expression.

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Acknowledgements

We thank F Lehembre, A Dejean and RT Hay for the gift of recombinants, members of the Wasylyk laboratory for their friendly help, support and encouragement, and the IGBMC core services. We acknowledge for financial assistance: the Association pour la Recherche sur le Cancer, Aventis, the Ligue Nationale Française contre le Cancer (Equipe labellisée), the Ligue Régionale (Haut-Rhin) contre le Cancer, the Ligue Régionale (Bas-Rhin) contre le Cancer, the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médicale, the Hôpital Universitaire de Strasbourg, and the European Union (FP5 project QLK6-2000-00159).

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Correspondence to Bohdan Wasylyk.

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Wasylyk, C., Criqui-Filipe, P. & Wasylyk, B. Sumoylation of the net inhibitory domain (NID) is stimulated by PIAS1 and has a negative effect on the transcriptional activity of Net. Oncogene 24, 820–828 (2005). https://doi.org/10.1038/sj.onc.1208226

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