The WW-HECT protein Smurf2 interacts with the Docking Protein NEDD9/HEF1 for Aurora A activation

Authors

Finola E. Moore, University Feinberg
Evan C. Osmundson, Northwestern University
Jennifer Koblinski, Northwestern University
Elena Pugacheva, West Virginia University
Erica A. Golemis, Fox Chase Cancer Center
Sipankar Ray, Northwestern University
Hiroaki Kiyokawa, Northwestern University

Author ORCID Identifier

N/A

N/A

https://orcid.org/0000-0002-7156-2030

https://orcid.org/0000-0001-9814-7446

https://orcid.org/0000-0001-9814-7446

N/A

https://orcid.org/0000-0002-7942-6455

Document Type

Article

Publication Date

2010

College/Unit

Eberly College of Arts and Sciences

Department/Program/Center

Biochemistry

Abstract

The multi-functional adaptor protein NEDD9/HEF1/Cas-L regulates cell motility, invasion and cell cycle progression, and plays key roles in cancer progression and metastasis. NEDD9 is localized to the centrosome and is required for activation of Aurora A kinase in mitosis. Here we demonstrate that the HECT-WW protein Smurf2 physically associ- ates with NEDD9 and is required for the stability of NEDD9 protein. Smurf2 depletion results in a marked decrease in NEDD9 protein levels, by facilitating polyubiquitination and proteasomal degradation of NEDD9. Conversely, forced overexpression of Smurf2 results in upregulation of endogenous NEDD9 protein, confirming the role for Smurf2 in NEDD9 stability. Cells with Smurf2 depletion fail to activate Aurora A at the G2/M boundary, leading to a marked delay in mitotic entry. These observations suggest that the stable complex of Smurf2 and NEDD9 is required for timely entry into mitosis via Aurora A activation.

Digital Commons Citation

Moore, Finola E.; Osmundson, Evan C.; Koblinski, Jennifer; Pugacheva, Elena; Golemis, Erica A.; Ray, Sipankar; and Kiyokawa, Hiroaki, "The WW-HECT protein Smurf2 interacts with the Docking Protein NEDD9/HEF1 for Aurora A activation" (2010). Faculty & Staff Scholarship. 2759.
https://researchrepository.wvu.edu/faculty_publications/2759

Source Citation

Moore, F.E., Osmundson, E.C., Koblinski, J. et al. The WW-HECT protein Smurf2 interacts with the Docking Protein NEDD9/HEF1 for Aurora A activation. Cell Div 5, 22 (2010). https://doi.org/10.1186/1747-1028-5-22

Comments

© 2010 Moore et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.