School of Medicine Publications and Presentations
Document Type
Article
Publication Date
2020
Abstract
In this study, we provide critical evidence that STAT2 stability regulation plays an essential role in melanoma cell proliferation and colony growth. We found that the interaction of FBXW7 and STAT2 induced STAT2 destabilization via a ubiquitination-mediated proteasomal degradation pathway. Notably, GSK3β-mediated STAT2 phosphorylation facilitated STAT2–FBXW7 interactions via the DNA binding domain of STAT2 and domains 1, 2, 6, and 7 of FBXW7 WD40. Importantly, the inverse correlation between protein levels of STAT2 and FBXW7 were observed not only in human melanoma cells but also in a human skin cancer tissue array. The relationship between protein levels of STAT2 and FBXW7, cell proliferation, and colony growth were similarly observed in the melanoma cell lines SK-MEL-2, -5, and -28. Moreover, STAT2 knockdown in melanoma cells suppressed melanoma cell proliferation and colony formation. These data demonstrated that FBXW7-mediated STAT2 stability regulation plays an essential role in melanoma cell proliferation and cancer growth.
Recommended Citation
Lee, C. J., An, H. J., Kim, S. M., Yoo, S. M., Park, J., Lee, G. E., ... & Cho, Y. Y. (2020). FBXW7-mediated stability regulation of signal transducer and activator of transcription 2 in melanoma formation. Proceedings of the National Academy of Sciences, 117(1), 584-594. https://doi.org/10.1073/pnas.1909879116
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Publication Title
Proceedings of the National Academy of Sciences
DOI
10.1073/pnas.1909879116
Academic Level
faculty
Comments
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).