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Open Access Research article

Importin alpha binding and nuclear localization of PARP-2 is dependent on lysine 36, which is located within a predicted classical NLS

Sandra S Haenni1, Matthias Altmeyer1, Paul O Hassa12, Taras Valovka13, Monika Fey1 and Michael O Hottiger1*

Author affiliations

1 Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland

2 European Molecular Biology Laboratory (EMBL), Gene Expression Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany

3 Institute of Biochemistry, University of Innsbruck, Peter-Mayr-Strasse 1a, 6020 Innsbruck, Austria

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Citation and License

BMC Cell Biology 2008, 9:39  doi:10.1186/1471-2121-9-39

Published: 21 July 2008

Abstract

Background

The enzymes responsible for the synthesis of poly-ADP-ribose are named poly-ADP-ribose polymerases (PARP). PARP-2 is a nuclear protein, which regulates a variety of cellular functions that are mainly controlled by protein-protein interactions. A previously described non-conventional bipartite nuclear localization sequence (NLS) lies in the amino-terminal DNA binding domain of PARP-2 between amino acids 1–69; however, this targeting sequence has not been experimentally examined or validated.

Results

Using a site-directed mutagenesis approach, we found that lysines 19 and 20, located within a previously described bipartite NLS, are not required for nuclear localization of PARP-2. In contrast, lysine 36, which is located within a predicted classical monopartite NLS, was required for PARP-2 nuclear localization. While wild type PARP-2 interacted with importin α3 and to a very weak extent with importin α1 and importin α5, the mutant PARP-2 (K36R) did not interact with importin α3, providing a molecular explanation why PARP-2 (K36R) is not targeted to the nucleus.

Conclusion

Our results provide strong evidence that lysine 36 of PARP-2 is a critical residue for proper nuclear targeting of PARP-2 and consequently for the execution of its biological functions.