کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10914748 | 1088810 | 2014 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
SUMOylation of RhoGDIα is required for its repression of cyclin D1 expression and anchorage-independent growth of cancer cells
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کلمات کلیدی
CDKGTPSUMOERKCyclin D1SUMOylationGEFsGDISsmall ubiquitin-related modifier - اصلاح کننده کوچک کوچک ubiquitingrowth arrest - دستگیری رشدAnchorage-independent growth - رشد مستقل لنگرگاهMEK - مجاهدین خلقMAP kinase - کیناز MAPcyclin-dependent kinase - کییناز وابسته به سیکلینGuanosine triphosphate - گوانوزین تری فسفات
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Selective activation of Rho GTPase cascade requires the release of Rho from RhoGDI (GDP-dissociation inhibitors) complexes. Our previous studies identified RhoGDIα SUMOylation at Lys-138 and its function in the regulation of cancer cell invasion. In the current study, we demonstrate that RhoGDIα SUMOylation has a crucial role in the suppression of cancer cell anchorage-independent growth as well as the molecular mechanisms underlying this suppression. We found that ectopic expression of RhoGDIα resulted in marked inhibition of an anchorage-independent growth with induction of G0/G1 cell cycle arrest, while point mutation of RhoGDIα SUMOylation at residue Lys-138 (K138R) abrogated this growth suppression and G0/G1 cell cycle arrest in cancer cells. Further studies showed that SUMOylation at Lys-138 was critical for RhoGDIα down-regulation of cyclin D1 protein expression and that MEK1/2-Erk was a specific downstream target of SUMOylated RhoGDIα for its inhibition of C-Jun/AP-1 cascade, cyclin d1 transcription, and cell cycle progression. These results strongly demonstrate that SUMOylated RhoGDIα suppressed C-Jun/AP-1-dependent transactivation specifically via targeting MEK1/2-Erk, subsequently leading to the down-regulation of cyclin D1 expression and anti-cancer activity. Our results provide new mechanistic insights into the understanding of essential role of SUMOylation at Lys-138 in RhoGDIα's biological function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Oncology - Volume 8, Issue 2, March 2014, Pages 285-296
Journal: Molecular Oncology - Volume 8, Issue 2, March 2014, Pages 285-296
نویسندگان
Zipeng Cao, Xueyong Li, Jingxia Li, Beipei Kang, Jingyuan Chen, Wenjing Luo, Chuanshu Huang,