Functional analysis of a ligand-dependent protein degradation system

为了揭示脂溶配体调节蛋白质表达的新机制，本研究对“配体依赖的蛋白质降解系统”进行了研究。以雌激素为配体，对雌激素信号传导中的降解底物进行了鉴定和功能分析。结果，有丝分裂关键调控因子通过泛素-蛋白酶体系统以雌激素依赖的方式降解。此外，研究还表明，雌激素促进了有丝分裂向G1期的转变。这些结果表明，雌激素通过促进有丝分裂调节剂在M期的降解而参与有丝分裂调控。本研究表明，雌激素通过两条途径调控靶蛋白水平，即与M/G1期相关的蛋白质降解和G1/S期众所周知的基因表达途径，为揭示雌激素信号转导机制提供了新的视角。

In this study, to reveal the novel mechanism of fat-soluble ligands regulating the proper protein expression, "Ligand-dependent protein degradation system" was investigated. Estrogen focused on as a ligand, the identification and functional analysis of the degradation substrates in an estrogen signaling was performed. As a result, the mitotic key regulator was degraded through Ubiquitin-proteasome system in an estrogen-dependent manner. moreover, it was shown that estrogen accelerated transition from mitosis to G1 phase. These results suggest that estrogen is related in the mitotic regulations through promoting the degradation of mitotic reugulator at M phase.This study shows that estrogen regulates target proteins level through two pathway, the protein degradation related in M/G1 phase and well known gene expression pathway in G1/S phase, providing a new insight into the mechanism of the estrogen signaling.