2011.04.21,Professor Wang Guanghui Published a paper entitled“The ER-associated degradation system regulates aggregation and degradation of mutant neuroserpin” in JBC

  • Author:Ying Zheng,Wang Hongfen,Fan Huadong,Wang Guanghui


    Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a neurodegenerative disorder characterized by the accumulation of neuroserpin polymers in the endoplasmic reticulum (ER) of cortical and subcortical neurons in the central nervous system (CNS) due to neuroserpin point mutations. ER-associated degradation (ERAD) is involved in mutant neuroserpin degradation. In this study, we demonstrate that two ER-associated E3 ligases, Hrd1 and gp78, are involved in the ubiquitination and degradation of mutant neuroserpin. Overexpression of Hrd1 and gp78 decreases mutant neuroserpin protein level, whereas Hrd1 and gp78 knockdown increases mutant neuroserpin stability. Moreover, ERAD impairment by mutant valosin-containing protein (VCP) increases mutant neuroserpin protein level and aggregate formation. Thus, these findings identify mutant neuroserpin as an ERAD target and show that Hrd1 and gp78 mediate mutant neuroserpin turnover through the ERAD pathway.


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