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IRES-dependent translational control of Cbfa1/Runx2 expression 总被引:4,自引:0,他引:4
The P1 and P2 promoters of the Cbfa1/Runx2 gene produce Type I and II mRNAs with distinct complex 5'-untranslated regions, respectively designated UTR1 and UTR2. To evaluate whether the 5'-UTRs impart different translational efficiencies to the two isoforms, we created SV40 promoter-UTR-luciferase reporter (luc) constructs in which the translational potential of the 5'-UTR regions was assessed indirectly by measurement of luciferase activity in transfected cell lines in vitro. In MC3T3-E1 pre-osteoblasts, UTR2 was translated approximately twice as efficiently as the splice variants of UTR1, whereas translation of unspliced UTR1 was repressed. To determine if the UTRs conferred internal ribosome entry site (IRES)-dependent translation, we tested bicistronic SV40 promoter-Rluc-UTR-Fluc constructs in which Fluc is expressed only if the intercistronic UTR permits IRES-mediated translation. Transfection of bicistronic constructs into MC3T3-E1 osteoblasts demonstrated that both UTR2 and the spliced forms of UTR1 possess IRES activity. Similar to other cellular IRESs, activity increased with genotoxic stress induced by mitomycin C. In addition, we observed an osteoblastic maturation-dependent increase in IRES-mediated translation of both UTR2 and the spliced forms of UTR1. These findings suggest that Cbfa1 UTRs have IRES-dependent translational activities that may permit continued Cbfa1 expression under conditions that are not optimal for cap-dependent translation. 相似文献
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Characterization of the upstream mouse Cbfa1/Runx2 promoter 总被引:9,自引:0,他引:9
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Cbfa1/Runx2与成骨细胞分化调控 总被引:9,自引:0,他引:9
成骨细胞是由间充质干细胞经骨原细胞和前成骨细胞分化而来的。近年来已鉴定转录因子Cbfal(core binding factor α1)是成骨细胞分化和骨形成的关键调控因子。在成骨细胞分化的过程中,Cbfal通过调控成骨细胞特异性细胞外基质蛋白基因的表达和成骨细胞周期参与成骨细胞的分化过程。新近发现Cbfal能通过自身的PST序列区域与Smads结合形成复合物共同参与成骨细胞的分化调控。 相似文献
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Expression of the osteoblast differentiation factor RUNX2 (Cbfa1/AML3/Pebp2alpha A) is inhibited by tumor necrosis factor-alpha. 总被引:8,自引:0,他引:8
Linda Gilbert Xiaofei He Paul Farmer Janet Rubin Hicham Drissi Andre J van Wijnen Jane B Lian Gary S Stein Mark S Nanes 《The Journal of biological chemistry》2002,277(4):2695-2701
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Overlapping expression of Runx1(Cbfa2) and Runx2(Cbfa1) transcription factors supports cooperative induction of skeletal development 总被引:3,自引:0,他引:3
Smith N Dong Y Lian JB Pratap J Kingsley PD van Wijnen AJ Stein JL Schwarz EM O'Keefe RJ Stein GS Drissi MH 《Journal of cellular physiology》2005,203(1):133-143
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Drissi H Pouliot A Koolloos C Stein JL Lian JB Stein GS van Wijnen AJ 《Experimental cell research》2002,274(2):323-333
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Tissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2 总被引:19,自引:0,他引:19
Zelzer E Glotzer DJ Hartmann C Thomas D Fukai N Soker S Olsen BR 《Mechanisms of development》2001,106(1-2):97-106
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S Sudhakar Y Li M S Katz N Elango 《Biochemical and biophysical research communications》2001,289(2):616-622