共查询到20条相似文献,搜索用时 15 毫秒
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Koinuma D Shinozaki M Nagano Y Ikushima H Horiguchi K Goto K Chano T Saitoh M Imamura T Miyazono K Miyazawa K 《The Journal of biological chemistry》2011,286(37):32502-32512
Transforming growth factor-β (TGF-β) signaling is controlled by a variety of regulators, of which Smad7, c-Ski, and SnoN play a pivotal role in its negative regulation. Arkadia is a RING-type E3 ubiquitin ligase that targets these negative regulators for degradation to enhance TGF-β signaling. In the present study we identified a candidate human tumor suppressor gene product RB1CC1/FIP200 as a novel positive regulator of TGF-β signaling that functions as a substrate-selective cofactor of Arkadia. Overexpression of RB1CC1 enhanced TGF-β signaling, and knockdown of endogenous RB1CC1 attenuated TGF-β-induced expression of target genes as well as TGF-β-induced cytostasis. RB1CC1 down-regulated the protein levels of c-Ski but not SnoN by enhancing the activity of Arkadia E3 ligase toward c-Ski. Substrate selectivity is primarily attributable to the physical interaction of RB1CC1 with substrates, suggesting its role as a scaffold protein. RB1CC1 thus appears to play a unique role as a modulator of TGF-β signaling by restricting substrate specificity of Arkadia. 相似文献
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Briones-Orta MA Sosa-Garrocho M Moreno-Alvarez P Fonseca-Sánchez MA Macías-Silva M 《Biochemical and biophysical research communications》2006,341(3):889-894
SnoN and Ski oncoproteins are co-repressors for Smad proteins and repress TGF-beta-responsive gene expression. The smad7 gene is a TGF-beta target induced by Smad signaling, and its promoter contains the Smad-binding element (SBE) required for a positive regulation by the TGF-beta/Smad pathway. SnoN and Ski co-repressors also bind SBE but regulate negatively smad7 gene. Ski along with Smad4 binds and represses the smad7 promoter, whereas the repression mechanism by SnoN is not clear. Ski and SnoN overexpression inhibits smad7 reporter expression induced through TGF-beta signaling. Using chromatin immunoprecipitation assays, we found that SnoN binds smad7 promoter at the basal condition, whereas after a short TGF-beta treatment for 15-30 min SnoN is downregulated and no longer bound smad7 promoter. Interestingly, after a prolonged TGF-beta treatment SnoN is upregulated and returns to its position on the smad7 promoter, functioning probably as a negative feedback control. Thus, SnoN also seems to regulate negatively the TGF-beta-responsive smad7 gene by binding and repressing its promoter in a similar way to Ski. 相似文献
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The transforming activity of Ski and SnoN is dependent on their ability to repress the activity of Smad proteins 总被引:12,自引:0,他引:12
He J Tegen SB Krawitz AR Martin GS Luo K 《The Journal of biological chemistry》2003,278(33):30540-30547
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Degradation of SnoN is thought to play an important role in the transactivation of TGF-beta responsive genes. We demonstrate that the anaphase-promoting complex (APC) is a ubiquitin ligase required for the destruction of SnoN and that the APC pathway is regulated by TGF-beta. The destruction box of SnoN is required for its degradation in response to TGF-beta signaling. Furthermore, the APC activator CDH1 and Smad3 synergistically regulate SnoN degradation. Under these circumstances, CDH1 forms a quaternary complex with SnoN, Smad3, and APC. These results suggest that APC(CDH1) and SnoN play central roles in regulating growth through the TGF-beta signaling system. 相似文献
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Activation of transforming growth factor-beta signaling by SUMO-1 modification of tumor suppressor Smad4/DPC4 总被引:15,自引:0,他引:15
Lin X Liang M Liang YY Brunicardi FC Melchior F Feng XH 《The Journal of biological chemistry》2003,278(21):18714-18719
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Harada J Kokura K Kanei-Ishii C Nomura T Khan MM Kim Y Ishii S 《The Journal of biological chemistry》2003,278(40):38998-39005