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COPS5 activates BMP. 13 / 13
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"Thus, aberrant accumulation of Jab1 resulting from inactivation of the CUL4B E3 ligase may enhance BMP signaling by decreasing levels of the inhibitor Smad7.For the structural basis, Jab1 ubiquitinati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Jab1 likely promotes Sox9 and BMP signaling activity during early limb development."
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"Previously we showed that Jab1 selectively modulates BMP signaling in chondrocytes and osteochondro-progenitor cells in vivo ( Bashur et al ., 2014 ; Chen et al ., 2013 ) ."
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"Our previous study in Prx1-cre; Jab1 mice showed that Jab1 positively regulates BMP signaling in osteochondral progenitor cells (15)."
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"However , it remains to be determined how Jab1 modulates BMP signaling in chondrocytes ."
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"As shown in XREF_FIG, Panels A and B, we observed a reduced level of Jab1 protein and an elevated level of BMP induced alkaline phosphatase mRNA, respectively, in C2C12 cells treated with Jab1 siRNA."
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"Consistent with the results shown in Fig. 1 A and B, the transfection of pFLAG-CUL4B could almost completely rescue the BMP signaling in RNAi mediated CUL4B depletion cells, whereas FLAG-CUL4A or FLAG[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Jab1 cKO chondrocytes displayed increased apoptosis, accelerated chondrocyte hypertrophy, G2 phase cell cycle arrest, and increased BMP response (Chen et al., 2013)."
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"And the upregulation of BMP signaling in response to CUL4B silencing could be partially rescued by co-depletion of Jab1, thus restoring BMP signaling to a level not significantly different from that o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Together, these data establish Jab1 as an ubiquitination target for the CUL4B ubiquitin ligase complex.In addition to its role in deneddylation [32,33], Jab1 and CSN5 has been shown to bind to Smad7, [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Previously we showed that Jab1 selectively modulates BMP signaling in chondrocytes and osteochondro-progenitor cells in vivo (Bashur et al., 2014; Chen et al., 2013)."
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"These observations suggest that Jab1 may promote BMP signaling in OPCs during early limb development."
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"However, it remains to be determined how Jab1 modulates BMP signaling in chondrocytes."
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