Study of the regulatory mechanism of ETAR and ETBR level by receptor binding protein and the relevance between clinical significance and endothelin receptor level.

我们鉴定了Jab 1作为内皮素受体（ET_AR和ET_BR）的C-尾结合蛋白，并表明Jab 1通过ETRs的泛素化调节受体水平。我们还发现，ET-1刺激后，ET_BR的泛素化水平增加。此外，我们还发现ET-1诱导的ET_BR内化需要泛素化。因此，我们已经证明，泛素化在调控ETRs的运输中具有重要作用。

We identified Jab1 as a C-tail binding protein of endothelin receptors (ETRs), including ET_AR and ET_BR and showed that Jab1 regulates receptor levels via ubiquitination of ETRs. We also found that ubiquitination level of ET_BR was increased upon endothelin-1 (ET-1) stimulation. Moreover, we indicated that the ubiquitination was required for ET-1-induced ET_BR internalization. Thus, we have demonstrated that ubiquitination has an important role in the regulation of trafficking of ETRs.