A critical step for JNK activation: isomerization by the prolyl isomerase Pin1
- Authors
- Park, J. E.; Lee, J. A.; Park, S. G.; Lee, D. H.; Kim, S. J.; Kim, H-J; Uchida, C.; Uchida, T.; Park, B. C.; Cho, S.
- Issue Date
- Jan-2012
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- c-Jun N-terminal kinase; peptidyl-prolyl cis/trans-isomerase; apoptosis
- Citation
- CELL DEATH AND DIFFERENTIATION, v.19, no.1, pp 153 - 161
- Pages
- 9
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Volume
- 19
- Number
- 1
- Start Page
- 153
- End Page
- 161
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/20602
- DOI
- 10.1038/cdd.2011.82
- ISSN
- 1350-9047
1476-5403
- 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 (2012) 19, 153-161; doi:10.1038/cdd.2011.82; published online 10 June 2011
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Pharmacy > School of Pharmacy > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/20602)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.