Fbxl18 targets LRRK2 for proteasomal degradation and attenuates cell toxicity

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• 作者：Xiaodong Ding^a ; ¹ ; Sandeep K. Barodia^b ; Lisha Ma^a ; Matthew S. Goldberg^a ; ^b ; ^{mattgoldberg@uab.edu}
• 关键词：LRRK2 ; Kinase ; Cell death
• 刊名：Neurobiology of Disease
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：98
• 期：Complete
• 页码：122-136
• 全文大小：6308 K
• 卷排序：98

文摘

We identified a novel protein, Fbxl18, that associates with LRRK2 and targets LRRK2 for degradation by the proteasome. We demonstrate that phosphorylation of LRRK2 is required for Fbxl18 to bind to LRRK2 and to promote LRRK2 degradation. siRNA-knockdown of endogenous Fbxl18 increases levels of endogenous LRRK2 while Fbxl18 overexpression decreases LRRK2. Increasing or decreasing Fbxl18 mitigates or enhances LRRK2-mediated cell toxicity.