کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2779538 1153274 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ubc9 negatively regulates BMP-mediated osteoblastic differentiation in cultured cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
Ubc9 negatively regulates BMP-mediated osteoblastic differentiation in cultured cells
چکیده انگلیسی

SUMO (small ubiquitin-related modifier) modification (SUMOylation) has been reported to regulate various biological events such as cell-cycle progression, proliferation, and survival. Bone morphogenetic proteins (BMPs) play an important role in osteoblast differentiation and maturation. Although Smad4, which acts as a transcriptional factor in the BMP signaling, is a target of SUMOylation, the involvement of SUMOylation in osteoblast differentiation remains unclear. In this report, we demonstrated spatial expression patterns of SUMO proteins and Ubc9 (ubiquitin conjugating enzyme 9), which is a unique E2-SUMOylation enzyme, in mouse tibia. Furthermore, siRNA knockdown of Ubc9 enhanced osteoblastic differentiation induced by BMP2 in C2C12 mouse myoblasts and ST2 mouse bone-marrow derived stromal cells. Ubc9 knockdown elevated the BMP signaling transduction and reduced the expression of muscle-related genes in cooperation with BMP2. Finally, a luciferase assay using an Id1 (target gene of BMP signaling) reporter revealed that Smad4 mutants prevented from SUMOylation at their Lys158 possessed more potent transcriptional activity than wild-type Smad4. Taken together, these findings suggest that Ubc9 negatively regulates osteoblastic differentiation induced by BMP via, at least in part, SUMOylation of Smad4.


► siRNA knockdown of Ubc9 enhanced BMP2-induced osteoblastic differentiation in C2C12 cells.
► Reporter assay showed that Ubc9 knockdown directly enhances the BMP signal transduction.
► Inhibition of SUMOylation of Smad4 elevated its transcriptional activity.
► Our data suggest that SUMOylation negatively regulated BMP-induced osteoblastic differentiation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 50, Issue 5, May 2012, Pages 1092–1099
نویسندگان
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