A critical step for JNK activation: isomerization by the prolyl isomerase Pin1 = 정크 활성화에 중요한 단계인 핀1에의한 이성체화

Cited 23 time in scopus
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Title
A critical step for JNK activation: isomerization by the prolyl isomerase Pin1 = 정크 활성화에 중요한 단계인 핀1에의한 이성체화
Author(s)
J E Park; J A Lee; Sung Goo Park; D H Lee; Seung Jun Kim; H J Kim; C Uchida; T Uchida; Byoung Chul Park; S Cho
Bibliographic Citation
Cell Death and Differentiation, vol. 19, no. 1, pp. 153-161
Publication Year
2012
Abstract
c-Jun N-terminal kinase (JNK) is activated by dual phosphorylation of both threonine and tyrosine residues in the phosphorylation loop of the protein in response to several stress factors. However, the precise molecular mechanisms for activation after phosphorylation remain elusive. Here we show that Pin1, a peptidyl-prolyl isomerase, has a key role in the JNK1 activation process by modulating a phospho-Thr-Pro motif in the phosphorylation loop. Pin1 overexpression in human breast cancer cell lines correlates with increased JNK activity. In addition, small interfering RNA (siRNA) analyses showed that knockdown of Pin1 in a human breast cancer cell line decreased JNK1 activity. Pin1 associates with JNK1, and then catalyzes prolyl isomerization of the phospho-Thr-Pro motif in JNK1 from trans- to cis-conformation. Furthermore, Pin1 enhances the association of JNK1 with its substrates. As a result, Pin1 -/- cells are defective in JNK activation and resistant to oxidative stress. These results provide novel insights that, following stress-induced phosphorylation of Thr in the Thr-Pro motif of JNK1, JNK1 associates with Pin1 and undergoes conformational changes to promote the binding of JNK1 to its substrates, resulting in cellular responses from extracellular signals.Cell Death and Differentiation advance online publication, 10 June 2011; doi:10.1038/cdd.2011.82.
Keyword
apoptosisc-Jun N-terminal kinasepeptidyl-prolyl cis/trans-isomerase
ISSN
1350-9047
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/cdd.2011.82
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
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