TPA-induced cell transformation provokes a complex formation between Pin1 and 90 kDa ribosomal protein S6 kinase 2
- Authors
- Cho, Young Sik; Park, Seung Yeon; Kim, Dong Joon; Lee, Sang-Han; Woo, Kee-Min; Lee, Kyung-Ae; Lee, Yoon-Jin; Cho, Yong-Yeon; Shim, Jung-Hyun
- Issue Date
- Aug-2012
- Publisher
- Kluwer Academic/Plenum Publishers
- Keywords
- Ribosomal S6 kinase 2; Peptidyl cis/trans prolyl isomerase; Tumorigenesis; 12-O-tetradecanoylphorbol-13-acetate; Post-translational modification
- Citation
- Molecular and Cellular Biochemistry, v.367, no.1-2, pp 85 - 92
- Pages
- 8
- Journal Title
- Molecular and Cellular Biochemistry
- Volume
- 367
- Number
- 1-2
- Start Page
- 85
- End Page
- 92
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/14982
- DOI
- 10.1007/s11010-012-1322-y
- ISSN
- 0300-8177
1573-4919
- Abstract
- Post-translational modification of peptidyl cis/trans prolyl isomerase Pin1 is crucial in regulation of gene stability. Pin1 phosphorylation at Ser(16) has been regarded as a marker for Pin1 isomerase activity and introduction of phosphorylation on Ser/Thr-Pro of substrate proteins is prerequisite for its binding activity with Pin1 and subsequent isomerization. Here, we found that 90 kDa ribosomal protein S6 kinase 2 (RSK2) could form a physical complex with Pin1, leading to phosphorylation of Pin1 at Ser(16) ex vivo and in vitro respectively. Intriguingly, Pin1(+/+) mouse embryonic fibroblasts (MEFs) exhibited significantly an increase in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced RSK2 phosphorylation with a marginal Pin1 phosphorylation compared with Pin1(-/-) MEFs. Moreover, TPA-induced Ser(16) Pin1 phosphorylation as well as RSK2 phosphorylation was considerably profound in RSK+/+ MEFs but not in RSK-/- MEFs. Consequently, knockdown of Pin1 using shRNA-Pin1 suppressed TPA-induced cell transformation in JB6 CI41 cells. Overall, these results indicate that Pin1 plays a critical role in TPA-induced tumorigenesis plausibly via physical interaction with RSK2 and reciprocal phosphorylation, therefore suggesting a potential therapeutic target for cancer treatment.
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Collections - College of Medicine > Department of Biochemistry > 1. Journal Articles
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