FBXW7-mediated stability regulation of signal transducer and activator of transcription 2 in melanoma formation.

In this study, we provide critical evidence that stability regulation plays an essential role in melanoma cell proliferation and colony growth. We found that the interaction of FBXW7 and duanyu18132 induced duanyu18132 destabilization via a ubiquitination-mediated proteasomal degradation pathway. Notably, GSK3β-mediated duanyu18132 phosphorylation facilitated interactions via the DNA binding domain of duanyu18132 and domains 1, 2, 6, and 7 of FBXW7 WD40. Importantly, the inverse correlation between protein levels of duanyu18132 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 duanyu18132 and FBXW7, cell proliferation, and colony growth were similarly observed in the melanoma cell lines SK-MEL-2, -5, and -28. Moreover, duanyu18132 knockdown in melanoma cells suppressed melanoma cell proliferation and colony formation. These data demonstrated that FBXW7-mediated duanyu18132 stability regulation plays an essential role in melanoma cell proliferation and cancer growth.

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