Essential Role of E2-25K/Hip-2 in Mediating Amyloid-β Neurotoxicity
In: Molecular Cell, Jg. 12 (2003-09-01), S. 553-563
Online
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Zugriff:
The ubiquitin/proteasome system has been proposed to play an important role in Alzheimer's disease (AD) pathogenesis. However, the critical factor(s) modulating both amyloid-beta peptide (Abeta) neurotoxicity and ubiquitin/proteasome system in AD are not known. We report the isolation of an unusual ubiquitin-conjugating enzyme, E2-25K/Hip-2, as a mediator of Abeta toxicity. The expression of E2-25K/Hip-2 was upregulated in the neurons exposed to Abeta(1-42) in vivo and in culture. Enzymatic activity of E2-25K/Hip-2 was required for both Abeta(1-42) neurotoxicity and inhibition of proteasome activity. E2-25K/Hip-2 functioned upstream of apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) in Abeta(1-42) toxicity. Further, the ubiquitin mutant, UBB+1, a potent inhibitor of the proteasome which is found in Alzheimer's brains, was colocalized and functionally interacted with E2-25K/Hip-2 in mediating neurotoxicity. These results suggest that E2-25K/Hip-2 is a crucial factor in regulating Abeta neurotoxicity and could play a role in the pathogenesis of Alzheimer's disease.
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Essential Role of E2-25K/Hip-2 in Mediating Amyloid-β Neurotoxicity
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Autor/in / Beteiligte Person: | Yates, Allan J. ; Hong, Yeon-Mi ; Soo Jung Seo ; Koh, Jae-Young ; Chul Woong Chung ; Kim, Soyoung ; Joo Yong Lee ; Jo, Dong-Gyu ; Yung Joon Yoo ; Sang Mi Shim ; Ichijo, Hidenori ; Song, Sungmin ; Min Chul Lee ; Jung, Yong-Keun |
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Zeitschrift: | Molecular Cell, Jg. 12 (2003-09-01), S. 553-563 |
Veröffentlichung: | Elsevier BV, 2003 |
Medientyp: | unknown |
ISSN: | 1097-2765 (print) |
DOI: | 10.1016/j.molcel.2003.08.005 |
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