Stress-induced oscillatory shuttling of Msn2 and Msn4 in and out the nucleus.
Cecilia Garmendia (1), Georges Renault (1), Sylvie Lallet (1), Albert Goldbeter (2), Michel Jacquet (1)
(1) IGM, Université Paris-Sud, bat 400, Orsay, 91405, France;
(2) Unité de Chronobiologie théorique, Faculté des Sciences, Université Libre de Bruxelles, B-1050 Brussels, Belgium
In the yeast Saccharomyces cerevisiae, a common set of genes is induced in response to various stresses or to reduction in nutritional availability. Most of these genes are controlled by the two partially redundant transcriptional activators Msn2 an Msn4. These proteins, mainly localized in the cytoplasm in glucose growing cells, are accumulated in the nucleus upon stress activation. This activation is negatively regulated by the activity of the cAMP-PKA and the TOR pathways. It is also associated with changes in phosphorylation. By using video-microscopy with GFP-tagged molecules, we have discovered that following activation, these transcription factors display an oscillatory shuttling behavior between cytoplasm and nucleus. Despite a large variation in periodicity between cells, within a given cell this phenomenon is synchronous at the molecular level (Jacquet, M., et al. (2003), J Cell Biol, 161: 497-505). However Msn2 and Msn4 are not synchronized in the same cell. In contrast to the known oscillatory behavior of transcription factors involving the synthesis of an inhibitor, this one is independent of the transcription and can occur with a protein deleted from its DNA binding domain and activating domain. By swapping NLS and NES with those of other nuclear proteins, we have identified a small region in Msn2, which is necessary and sufficient to promote oscillations.
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