【摘 要】
：
The membrane-anchored ubiquitin ligase gp78 promotes degradation of misfolded ER proteins and sterol-regulated degradation of HMG-CoA reductase.It was known before that Ufd1 plays a critical role in E
【机 构】
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State key laboratory of Molecular Biology,Institute of Biochemistry and Cell Biology,Shanghai Instit
【出 处】
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第六届海峡两岸生物医学和生物工程学术会议
论文部分内容阅读
The membrane-anchored ubiquitin ligase gp78 promotes degradation of misfolded ER proteins and sterol-regulated degradation of HMG-CoA reductase.It was known before that Ufd1 plays a critical role in ER-associated degradation (ERAD) together with Npl4 and VCP.The Ufd1-Npl4-VCP complex recognizes poly-ubiquitin chains and transfers the ubiquitinated proteins to proteasome.Here we show Ufd1 directly interacts with gp78 and functions as a cofactor.Ufd1 enhances the E3 activity of gp78,accelerates the ubiquitination and degradation of reductase,and eventually promotes receptor-mediated up-take of LDL.Furthermore,we identify that the mono-ubiquitin binding site in Ufd1 is required for the enhancement of gp78 activity; and the poly-ubiquitin binding site in Ufd1 is critical for a post-ubiquitination step in ERAD.In summary,our study identifies Ufd1 as a cofactor of gp78,reveals an unappreciated function of Ufd1 in ubiquitination reaction during ERAD,and illustrates that Ufd1 plays a critical role in cholesterol metabolism.
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