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Cellular and Molecular Life Sciences

, Volume 70, Issue 21, pp 4157–4168

First Online: 18 April 2013Received: 07 February 2013Revised: 19 March 2013Accepted: 02 April 2013DOI: 10.1007-s00018-013-1336-y

Cite this article as: Huber, P., Crum, T., Clary, L.M. et al. Cell. Mol. Life Sci. 2013 70: 4157. doi:10.1007-s00018-013-1336-y

Abstract

T-box transcription factors are critical developmental regulators in all multi-cellular organisms, and altered T-box factor activity is associated with a variety of human congenital diseases and cancers. Despite the biological significance of T-box factors, their mechanism of action is not well understood. Here we examine whether SUMOylation affects the function of the C. elegans Tbx2 sub-family T-box factor TBX-2. We have previously shown that TBX-2 interacts with the E2 SUMO-conjugating enzyme UBC-9, and that loss of TBX-2 or UBC-9 produces identical defects in ABa-derived pharyngeal muscle development. We now show that TBX-2 is SUMOylated in mammalian cell assays, and that both UBC-9 interaction and SUMOylation depends on two SUMO consensus sites located in the T-box DNA binding domain and near the TBX-2 C-terminus, respectively. In co-transfection assays, a TBX-2:GAL4 fusion protein represses expression of a 5xGal4:tk:luciferase construct. However, this activity does not require SUMOylation, indicating SUMO is not generally required for TBX-2 repressor activity. In C. elegans, reducing SUMOylation enhances the phenotype of a temperature-sensitive tbx-2 mutant and results in ectopic expression of a gene normally repressed by TBX-2, demonstrating that SUMOylation is important for TBX-2 function in vivo. Finally, we show mammalian orthologs of TBX-2, Tbx2, and Tbx3, can also be SUMOylated, suggesting SUMOylation may be a conserved mechanism controlling T-box factor activity.

KeywordsT-box SUMOylation C. elegans TBX-2 Genetic enhancer Electronic supplementary materialThe online version of this article doi:10.1007-s00018-013-1336-y contains supplementary material, which is available to authorized users.

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Autor: Paul Huber - Tanya Crum - Lynn M. Clary - Tom Ronan - Adelaide V. Packard - Peter G. Okkema

Fuente: https://link.springer.com/







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