DNA damage-induced translocation of S100A11 into the nucleus regulates cell proliferation
1 Core Unit Chip Application (CUCA), Institute of Human Genetics and Anthropology, University Hospital Jena, 07740 Jena, Germany
2 Department of Molecular Biology, Fritz Lipmann Institut (FLI) - Leibniz Institute for Age Research, 07743 Jena, Germany
3 Current Address: Abt. Molekulare Onkologie, Universitätsmedizin Göttingen, Georg-August-Universität, 37077 Göttingen, Germany
4 Current Address: Membrane Trafficking Group; Fritz Lipmann Institut (FLI) - Leibniz Institute for Age Research, 07743 Jena, Germany
5 Current Address: Biomolecular Photonics Group, University Hospital Jena, 07740 Jena, Germany
BMC Cell Biology 2010, 11:100 doi:10.1186/1471-2121-11-100Published: 17 December 2010
Proteins are able to react in response to distinct stress stimuli by alteration of their subcellular distribution. The stress-responsive protein S100A11 belongs to the family of multifunctional S100 proteins which have been implicated in several key biological processes. Previously, we have shown that S100A11 is directly involved in DNA repair processes at damaged chromatin in the nucleus. To gain further insight into the underlying mechanism subcellular trafficking of S100A11 in response to DNA damage was analyzed.
We show that DNA damage induces a nucleolin-mediated translocation of S100A11 from the cytoplasm into the nucleus. This translocation is impeded by inhibition of the phosphorylation activity of PKCα. Translocation of S100A11 into the nucleus correlates with an increased cellular p21 protein level. Depletion of nucleolin by siRNA severely impairs translocation of S100A11 into the nucleus resulting in a decreased p21 protein level. Additionally, cells lacking nucleolin showed a reduced colony forming capacity.
These observations suggest that regulation of the subcellular distribution of S100A11 plays an important role in the DNA damage response and p21-mediated cell cycle control.