Constitutive nucleocytoplasmic transport of STAT1 and the regulation of transcription
Final Report Abstract
Altogether we consider this project a great success. We approached two significant problems – intranuclear mobility in general and transcription factor activation. We expect that especially the publication at Biophysical Journal will become a classic, because we were the first to image and analyze intracellular transcription factor activation at the single molecule level. To our knowledge at least four further groups are currently working hard on this problem of very general interest. Furthermore, the results on STAT1-importin interactions are also advancing the molecular understanding of extracellular-signaling to the nucleus, as is our examination of the alleged acetylation of the nuclear import signal of STAT1. The combination of state-of-the-art single molecule microscopy and cutting edge protein biochemistry and cell biology has proved extremely productive. Altogether, the collaboration was very fruitful, and we currently consider ways to extend it into the future. In essence this project has provided proof-of-principle data, showing that our joint expertise allows us to solve complex problems in the field of transcription factor activation that other groups cannot approach. The challenge ahead is now to link mobility in the nucleus, particularly immobilization at putative promoters, with the activation of actual transcription and RNA-polymerase recruitment.
Publications
- 2010. Molecular basis for the recognition of phosphorylated STAT1 by importin alpha5. J. Mol. Biol. 402:83-100
Nardozzi, J., N. Wenta, N. Yasuhara, U. Vinkemeier and G. Cingolani
- 2010. Single ovalbumin molecules exploring nucleoplasm and nucleoli of living cell nuclei. BBA – Mol. Cell Res. 1803: 396-404
Speil, J.C., and U. Kubitscheck
- 2011. STAT1 signalling is not regulated by a phosphorylation acetylation switch. Mol. Cell. Biol. 31:3029-3037
Antunes, F., A. Marg and U, Vinkemeier
