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Molecular Cancer

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Open Access 01-12-2008 | Research

The parafibromin tumor suppressor protein interacts with actin-binding proteins actinin-2 and actinin-3

Authors: Sunita K Agarwal, William F Simonds, Stephen J Marx

Published in: Molecular Cancer | Issue 1/2008

Abstract

Background

Germline and somatic inactivating mutations in the HRPT2 gene occur in the inherited hyperparathyroidism-jaw tumor syndrome, in some cases of parathyroid cancer and in some cases of familial hyperparathyroidism. HRPT2 encodes parafibromin. To identify parafibromin interacting proteins we used the yeast two-hybrid system for screening a heart cDNA library with parafibromin as the bait.

Results

Fourteen parafibromin interaction positive preys representing 10 independent clones encoding actinin-2 were isolated. Parafibromin interacted with muscle alpha-actinins (actinin-2 and actinin-3), but not with non-muscle alpha-actinins (actinin-1 and actinin-4). The parafibromin-actinin interaction was verified by yeast two-hybrid, GST pull-down, and co-immunoprecipitation. Yeast two-hybrid analysis revealed that the N-terminal region of parafibromin interacted with actinins. In actin sedimentation assays parafibromin did not dissociate skeletal muscle actinins from actin filaments, but interestingly, parafibromin could also bundle/cross-link actin filaments. Parafibromin was predominantly nuclear in undifferentiated proliferating myoblasts (C2C12 cells), but in differentiated C2C12 myotubes parafibromin co-localized with actinins in the cytoplasmic compartment.

Conclusion

These data support a possible contribution of parafibromin outside the nucleus through its interaction with actinins and actin bundling/cross-linking. These data also suggest that actinins (and actin) participate in sequestering parafibromin in the cytoplasmic compartment.

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Title: The parafibromin tumor suppressor protein interacts with actin-binding proteins actinin-2 and actinin-3
Authors: Sunita K Agarwal
William F Simonds
Stephen J Marx
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2008
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-7-65

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Background

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