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PPARγ E3 ubiquitin ligase regulates MUC1-C oncoprotein stability

Oncogene volume 33, pages 5619–5625 (2014)Cite this article

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Abstract

MUC1-C oncoprotein is associated with colon, breast, ovarian, lung and pancreatic cancers. MUC1-C interacts with intracellular proteins to elicit signaling cascades that induce cell proliferation and tumor growth. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ), an E3 ubiquitin ligase, is an inhibitor of MUC1-C-mediated cell proliferation. PPARγ does so by binding to and inducing MUC1-C proteasome-dependent degradation that was independent of PPARγ transcriptional activity. Lys134 residue was found to be critically important for PPARγ-mediated MUC1-C degradation, as it terminated MUC1-C-mediated cell proliferation. These findings demonstrate PPARγ induces MUC1-C ubiquitination and degradation that is critical to terminate MUC1-C signaling pathway-elicited cancer.

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Acknowledgements

This work was supported by Jiangsu Province Natural Science Foundation (SBK201320232) and Start Fund of University of JiangSu (12JDG071).

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  1. Institute of Life Science, JiangSu University, Zhenjiang, China

    Y Hou, J Gao, H Xu, Y Xu, Z Zhang, Q Xu & C Zhang

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  1. Y Hou
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Correspondence to Y Hou.

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Hou, Y., Gao, J., Xu, H. et al. PPARγ E3 ubiquitin ligase regulates MUC1-C oncoprotein stability. Oncogene 33, 5619–5625 (2014). https://doi.org/10.1038/onc.2013.504

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