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  • Original Article
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Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation

Oncogene volume 31, pages 1835–1844 (2012)Cite this article

Abstract

The c-Jun transcription factor is a highly unstable oncoprotein. Several ubiquitin ligases mediate c-Jun degradation. However, c-Jun can be stabilized once it is phosphorylated at the N-terminus by c-Jun N-terminal kinases (JNKs) or other protein kinases. This phosphorylation decreases c-Jun ubiquitination and degradation. The underlying mechanism for this phenomenon is still unknown. Here, we show that receptor for activated C-kinase 1 (Rack1) can bind with c-Jun and ubiquitin ligase Fbw7 to form a complex. When c-Jun is phosphorylated at the N-terminus, c-Jun is released from the complex and cannot be ubiquitinated by Fbw7, which leads to increased stabilization and accumulation of c-Jun. These results reveal that Rack1 has a very important role in tumorigenesis by maintaining the stability of c-Jun that has been phosphorylated at its N-terminus by JNKs or other kinases.

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Acknowledgements

We thank Dr Wang Luhai and Dr Ronai Ze’ev for providing the HA-FL-Rack1, HA-WD1-4-Rack1 and HA-WD5-7-Rack1 vectors and Dr Wei Wenyi for providing the Flag-wt-c-Jun, Flag-ΔJNK-c-Jun, Flag-AF-c-Jun and Flag-AF-ΔJNK-c-Jun plasmids. We also thank Dr Bohmann Dirk for providing the c-JunAla and c-JunAsp mutant c-Jun plasmids. This study was supported by The Hormel Foundation and National Institutes of Health grants CA077646, CA111536, CA120388, ES016548 and R37 CA081064.

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  1. J Zhang and F Zhu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA

    J Zhang, F Zhu, X Li, Y Xu, C Peng, S Li, Y-Y Cho, K Yao, T A Zykova, A M Bode & Z Dong

  2. Physiology and Pathophysiology, Basic Medical School, Zhengzhou University, Zhengzhou1, China,

    X Li & Z Dong

  3. College of Pharmacy, The Catholic University of Korea, Gyeonggi-Do, Republic of Korea

    Y-Y Cho

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  1. J Zhang
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Correspondence to Z Dong.

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Zhang, J., Zhu, F., Li, X. et al. Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation. Oncogene 31, 1835–1844 (2012). https://doi.org/10.1038/onc.2011.369

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