We developed methods for culture of cardiocytes from zebrafish embryos and found that, even in culture, cells from smo continue to beat relatively slowly.
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The peculiarity of smo....
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Thus, the differential phosphorylation of Smo mediates the thresholds of Hh activity.
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In addition, little is known about whether ubiquitination is involved in Smo regulation.
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Smo inhibitor particularly blocked the formation of hypertrophic chondrocytes and collagen type X expression.
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Moreover, we showed that Smurf-mediated Patched ubiquitination depends on Smo activity in wing discs.
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Here, we identify a novel feedback mechanism that regulates Smo through the Fu-Cos2 complex.
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Furthermore, these data support rational combinations of hypomethylating agents with SMO antagonists in clinical trials.
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The activation of Smo appears to be one of the most important events in Hh signaling.
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We show that SANTs and SAG exert opposite effects on Smo activity by regulating protein conformation.
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A longstanding question is how Ptc inhibits Smo and how such inhibition is relieved by Hh stimulation.
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Endogenous Smo accumulated upon ESCRT-III inactivation is highly activated, which is induced by phosphorylation but not sumoylation.
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Furthermore, we find that the levels of Smo cell-surface expression and activity correlate with its levels of phosphorylation.
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Mutating these serine residues attenuates the ability of Smo to transduce high level Hh signaling activity in vivo.
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Two additional cell lines both having one methylated SMO allele and expressing mutant SMO did not express GLI3.
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In summary, our study reveals a novel cell survival mechanism in which SMO stabilizes and protects TRAF6 from degradation.