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The M458L missense mutation disrupts the catalytic properties of Parkin
Author(s) -
Do YunJu,
Yun Seo Young,
Park MinYoung,
Kim Eunhee
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12934
Subject(s) - parkin , mutant , ubiquitin ligase , mutation , ubiquitin , neurodegeneration , missense mutation , pink1 , biology , transfection , microbiology and biotechnology , genetics , chemistry , mitophagy , apoptosis , cell culture , gene , parkinson's disease , disease , medicine , autophagy , pathology
Parkin encodes an E3 ubiquitin ligase, and mutations affecting its catalytic potential are implicated in autosomal recessive Parkinson's disease (PD). The M458L mutation of parkin and its enzymatic effects require characterization. Therefore, we examined the enzymatic activity of Parkin with M458L mutation. We show that the M458L mutant retains its autoubiquitination potential in vitro but not in cells. Fas‐associated factor 1 and p38 (substrates of Parkin) are able to bind to the M458L mutant in cells; however, these Parkin substrates are not ubiquitinated and degraded in M458L mutant‐transfected cells. Moreover, M458L mutant fails to protect the mitochondria against hydrogen peroxide , leading to cell death. Considering the role of mitochondrial dysfunction in PD pathogenesis, our results imply a causative role for the M458L mutation in neurodegeneration.