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- 저자 : Han-KyuLee (검색결과 2 건)
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Neddylation positively regulates the ubiquitin E3 ligase activity of parkin
Um, Ji Won,Han, Kyung Ah,Im, Eunju,Oh, Yohan,Lee, Kyule,Chung, Kwang Chul Wiley Subscription Services, Inc., A Wiley Company 2012 JOURNAL OF NEUROSCIENCE RESEARCH - Vol.90 No.5
<P><B>Abstract</B></P><P>Mutations in the parkin gene underlie a familial form of Parkinson's disease known as autosomal recessive juvenile Parkinsonism (AR‐JP). Dysfunction of parkin, a ubiquitin E3 ligase, has been implicated in the accumulation of ubiquitin proteasome system‐destined substrates and eventually leads to cell death. However, regulation of parkin enzymatic activity is incompletely understood. Here we investigated whether the ubiquitin E3 ligase activity of parkin could be regulated by neddylation. We found that parkin could be a target of covalent modification with NEDD8, a ubiquitin‐like posttranslational modifier. In addition, NEDD8 attachment caused an increase of parkin activity through the increased binding affinity for ubiquitin‐conjugating E2 enzyme as well as the enhanced formation of the complex containing parkin and substrates. These findings point to the functional importance of NEDD8 and suggest that neddylation is one to the diverse modes of parkin regulation, potentially linking it to the pathogenesis of AR‐JP. © 2012 Wiley Periodicals, Inc.</P>
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Seong-SooShoi,이진구,Eun-JungHan,Ki-JungHan,Han-KyuLee,JonghoLee,Hong-WonSuh 대한약학회 2003 Archives of Pharmacal Research Vol.26 No.5
Certain polycyclic aromatic hydrocarbons (PAHs) have been reported to induce cytochrome P450 (CYP) 1A1 and 1A2. In the present study, the effects of six well-known PAHs, such as benzo[a]pyrene, benz[a]anthracene, dibenz[a,h]anthracene, chrysene, benzo[k]fluorancene and benzo[b]fluorancene, on the activities of hepatic and pulmonary CYP enzymes were investigated in male ICR mice. When mice were treated intraperitoneally with 3, 10 and 30 mg/ kg of individual PAHs for 3 consecutive days, the activities of ethoxyresorufin- and methoxyresorufin- O-dealkylases were significantly and differentially induced in both liver and lung. Moreover, other CYP isozyme-associated monooxygenase activities were also induced significantly in liver and lung with characteristic induction profiles. Our present results suggest that individual PAHs might have inductive effects on CYP isozymes, and that the characteristic inductive effects of individual PAHs on certain CYP isozymes would be developed as a marker for determining exposure to certain PAHs.
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