Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-12466
Haenni, S S; Altmeyer, M; Hassa, P O; Valovka, T; Fey, M; Hottiger, M O (2008). Importin alpha binding and nuclear localization of PARP-2 is dependent on lysine 36, which is located within a predicted classical NLS. BMC Cell Biology, 9:39:1-11.
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 alpha3 and to a very weak extent with importin alpha1 and importin alpha5, the mutant PARP-2 (K36R) did not interact with importin alpha3, 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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||05 Vetsuisse Faculty > Institute of Veterinary Biochemistry and Molecular Biology|
|DDC:||570 Life sciences; biology|
|Date:||21 July 2008|
|Deposited On:||04 Feb 2009 09:33|
|Last Modified:||27 Nov 2013 19:49|
|Additional Information:||Free full text article|
|Citations:||Web of Science®. Times Cited: 1|
Scopus®. Citation Count: 1
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page