|
Type |
Poster Presentation |
Area |
Life Chemistry |
Room No. |
Event Hall |
Time |
4월 20일 (금요일) 11:00~12:30 |
Code |
BIO.P-276 |
Subject |
Regulatory roles of USP14 in autophagic flux and clearance of proteopathic proteins |
Authors |
Jung Hoon Lee, Min Jae Lee* College of Medicine, Biochemistry, Seoul National University, Korea |
Abstract |
Ubiquitin-proteasome system (UPS) and autophagy-lysosome system (ALS) are the two major pathway for eukaryotic intracellular protein degradation. These two protein degradation systems were regarded as independent pathway with few or no points of interaction. However, accumulating evidences have pointed that the UPS and ALS could affect each other’s activity. Here, we investigated the effects of upregulated ubiquitin-proteasome system (UPS) activity on the autophagy flux. Activated proteasome by inhibiting Usp14, a proteasome-associated deubiquitinating enzyme, resulted in impaired autophagy maturation at the autophagosome-lysosome fusion step. Facilitated proteasomal degradation of tau and alpha-synuclein by Usp14 inhibitors was beneficial to cells to reduce the level of its aggregated form. To the contrary, inclusion body formations of non-proteasome substrates such as huntingtin with long polyglutamine repeats was accelerated when Usp14 was inhibited, suggesting that Usp14 is a common denominators between UPS and autophagy with counter-functional activities. These results indicate that understanding these two protein clearance mechanisms contribute to the degradation of aggregation-prone proteins during the pathophysiological stages. |
E-mail |
jhlee7802@gmail.com |
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