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FBXW7-mediated stability regulation of signal transducer and activator of transcription 2 in melanoma formationopen access

Authors
Lee, Cheol-JungAn, Hyun-JungKim, Seung-MinYoo, Sun-MiPark, JuheeLee, Ga-EunKim, Woo-YoungKim, Dae JoonKang, Han ChangLee, Joo YoungLee, Hye SukCho, Sung-JunCho, Yong-Yeon
Issue Date
Jan-2020
Publisher
NATL ACAD SCIENCES
Keywords
FBXW7; STAT2; ubiquitination; protein stability; melanoma
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.117, no.1, pp 584 - 594
Pages
11
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume
117
Number
1
Start Page
584
End Page
594
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/2568
DOI
10.1073/pnas.1909879116
ISSN
0027-8424
1091-6490
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, GSK3 beta-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.
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