FOXL2 posttranslational modifications mediated by GSK3β determine the growth of granulosa cell tumours
作者： Jae-Hong Kim , Yong-Hak Kim , Hong-Man Kim , Ho-Oak Park , Nam-Chul Ha
DOI: 10.1038/NCOMMS3936
关键词:
摘要: Approximately 97% of patients with ovarian granulosa cell tumours (GCTs) bear the C134W mutation in FOXL2; however, pathophysiological mechanism this is unknown. Here we report how affects GCT development. Sequential posttranslational modifications mutant occur where hyperphosphorylation at serine 33 (S33) by GSK3β induces MDM2-mediated ubiquitination and proteasomal degradation. In contrast, S33 wild-type FOXL2 underphosphorylated, leading to its SUMOylation stabilization. This prominent also observed bearing mutation. xenograft mice, phosphorylation status correlates oncogenicity FOXL2, inhibition efficiently represses growth. These findings reveal a previously unidentified regulatory that determines oncogenic attributes via differential
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