- Cellular responses to stress.
- Transmission mechanisms of intracellular signals.
The Cell Signaling group is lead by F. Posas and E. de Nadal. The group tries to understand how cells detect and respond to environmental changes. They have focused their studies in the characterization of the osmo-stress signal transduction pathways, especially those controlled by MAP kinases of the Hog1/p38 family, also known as the stress activated MAP kinases (SAPK). Using the S. cerevisiae yeast as a model organism as well as higher eukaryotic cells, they analyze the molecular mechanisms of cells to respond to an extracellular stimulus and which are the generated adaptation responses. A proper adaptation to stress requires the modulation of several basic aspects of the cell biology. Among them, cell cycle and gene expression regulation. Recently, the group is also analyzing the basic signaling properties of the HOG pathway and how to alter them, and in the field of synthetic biology, they have implemented complex engineered networks to perform in vivo cellular computation.
Most relevant publications:
- Duch A, Felipe-Abrio I, Barroso S, Yaakov G, García-Rubio M, Aguilera A, Nadal E, Posas F*. Coordinated control of replication and transcription by a SAPK protects genomic integrity. Nature 493(7430):116-9 (2013).
- Nadal-Ribelles M, Conde N, Flores O, González-Vallinas J, Eyras E, Orozco M, de Nadal E*, Posas F*. Hog1 bypasses stress-mediated down-regulation of transcription by RNA polymerase II redistribution and chromatin remodeling. Genome Biol.; 13(11):R106 (2012).
- de Nadal E, Ammerer G, Posas F*. Controlling gene expression in response to stress. Nat Rev Genet.; 12(12):833-45. Review (2011).
- Solé C, Nadal-Ribelles M, Kraft C, Peter M, Posas F*, de Nadal E*. Control of Ubp3 ubiquitin protease activity by the Hog1 SAPK modulates transcription upon osmostress. EMBO J. 30(16):3274-84 (2011).
- Regot S, Macia J, Conde N, Peeters T, Kentaro F, Hohmann S., de Nadal E, Posas F*, Solé S*. Distributed Biological Computation with Multicellular Engineered Networks. Nature 469: 207-11 (2011).
- Pelet S, Rudolf F, Nadal-Ribelles M, de Nadal E, Posas F, Peter M. Transient activation of the HOG MAPK pathway regulates bimodal gene expression. Science 332(6030): 732-5 (2011).
- de Nadal, E.*, Posas, F.* Multilayered control of gene expression by stress-activated protein kinases. EMBO J. 29, 4-13 (2010).
- Macia, J., Regot, S., Peeters, T., Conde, N., Solé, R.*, Posas, F.* Dynamic signaling in the Hog1 MAPK pathway relies on high basal signal transduction. Sci Signal. 2, ra13 (2009).
- Mas, G., de Nadal, E., Dechant, R., Rodríguez de la Concepción, ML., Logie, C., Jimeno-González, S., Chávez, S., Ammerer, G.*, Posas, F.* Recruitment of a chromatin remodelling complex by the Hog1 MAP kinase to stress genes. EMBO J. 28, 326-336 (2009).
- Proft, M., Mas, G., de Nadal, E., Vendrell, A., Noriega, N., Struhl, K., Posas, F. The stress-activated Hog1 kinase is a selective transcriptional elongation factor for genes responding to osmotic stress. Mol Cell. 23, 241-50 (2006).
- Clotet, J., Escote, X., Adrover, MA., Yaakov, G., Gari, E., Aldea, M., de Nadal, E., Posas, F. Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity. EMBO J. 25, 2338-2346 (2006).
- Escoté, X., Zapater, M., Clotet, J., Posas, F. Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1. Nat. Cell. Biol., 6, 997-1002 (2004).
- de Nadal, E., Zapater, M., Alepuz, PM., Sumoy, L., Mas, G., Posas, F. The Hog1 MAP kinase recruits the Rpd3 histone deacetylase to activate osmoresponsive genes. Nature, 427, 370-374 (2004).
- Alepuz, PM., de Nadal, E., Zapater, M., Ammerer, G., Posas, F. Osmostress-induced transcription by Hot1 depends on a Hog1-mediated recruitment of the RNA Pol II. EMBO J. 22, 2433-2442 (2003).
- Proft, M., Pascual-Ahuir, A., de Nadal, E., Arińo, J., Serrano, R., Posas, F.* Regulation of the Sko1 transcriptional repressor by the Hog1 MAP kinase in response to osmotic stress. EMBO J. 20, 1123-1133 (2001).
- Posas, F. & Saito, H. Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator. EMBO J., 17, 1385-1394 (1998).
- Posas, F. & Saito, H. Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK. Science, 276, 1702-1705 (1997).
- Posas, F., Wurgler-Murphy, SM., Maeda, T., Witten, EA., Thai, TC. & Saito, H. Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 "Two-component" osmosensor. Cell, 86, 865-875 (1996).