کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2108408 1083778 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mutations in Fbx4 Inhibit Dimerization of the SCFFbx4 Ligase and Contribute to Cyclin D1 Overexpression in Human Cancer
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Mutations in Fbx4 Inhibit Dimerization of the SCFFbx4 Ligase and Contribute to Cyclin D1 Overexpression in Human Cancer
چکیده انگلیسی

SummarySCFFbx4 was recently identified as the E3 ligase for cyclin D1. We now describe cell-cycle-dependent phosphorylation and dimerization of Fbx4 that is regulated by GSK3β and is defective in human cancer. We present data demonstrating that a pathway involving Ras-Akt-GSK3β controls the temporal phosphorylation and dimerization of the SCFFbx4 E3 ligase. Inhibition of Fbx4 activity results in accumulation of nuclear cyclin D1 and oncogenic transformation. The importance of this regulatory pathway for normal cell growth is emphasized by the prevalence of mutations in Fbx4 in human cancer that impair dimerization. Collectively, these data reveal that inactivation of the cyclin D1 E3 ligase likely contributes to cyclin D1 overexpression in a significant fraction of human cancer.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 14, Issue 1, 8 July 2008, Pages 68–78
نویسندگان
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