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Title 

Co-chaperone CHIP associates with mutant Cu/Zn-superoxide dismutase proteins linked to familial amyotrophic lateral sclerosis and promotes their degradation by proteasomes

Authors 

Jin Sun ChoiSayeon ChoSung Goo ParkByoung Chul ParkDo Hee Lee

Publisher 

Elsevier

Issue Date 

2004

Citation 

Biochemical and Biophysical Research Communications, vol. 321, no. 3, pp. 574-583

Keywords 

amyotrophic lateral sclerosisCHIPHsc70Hsp90proteasomeSOD1ubiquitincarboxyl terminus of heat shock protein 70 interacting proteinchaperonecopper zinc superoxide dismutase

Abstract 

Although the ubiquitin-proteasome system and the molecular chaperones are implicated to play an important role in pathogenesis of familial amyotrophic lateral sclerosis (FALS) caused by mutations in Cu/Zn-superoxide dismutase (SOD1), the mechanism underlying the causes of this fatal disease is still poorly understood. Here we found that co-chaperone CHIP (carboxyl terminus of Hsc70-interacting protein), together with molecular chaperones Hsc70/Hsp70 and Hsp90, associates with FALS-linked mutant SOD1 proteins in cultured human cells. S5a subunit of 26S proteasomes, which recognizes polyubiquitylated proteins, also interacts with mutant SOD1 proteins. Over-expression of CHIP leads to the reduction in cellular levels of mutant SOD1 as well as the suppression of cytotoxicity induced by mutant SOD1. Unusually, rather than increasing the level of poly-ubiquitylated SOD1, over-expressed CHIP alters the ubiquitylation pattern of mutant SOD1 proteins. Both down-regulation and ubiquitylation of mutant SOD1 are greatly reduced by a mutant CHIP protein lacking U-box domain. Taken together, these results suggest that co-chaperone CHIP, possibly with another E3 ligase(s), modulates the ubiquitylation of mutant SOD1 and renders them more susceptible for proteasomal degradation.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2004.07.010

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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