Pin1 plays a critical role as a molecular switch in canonical BMP signaling

Yoon, W-J, Islam, Rabia, Cho, Y-D, Ryu, K-M, Shin, H-R, Woo, K-M, Baek, J-H and Ryoo, H-M 2015, Pin1 plays a critical role as a molecular switch in canonical BMP signaling, Journal of cellular physiology, vol. 230, no. 3, pp. 640-647, doi: 10.1002/jcp.24787.

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Title Pin1 plays a critical role as a molecular switch in canonical BMP signaling
Author(s) Yoon, W-J
Islam, RabiaORCID iD for Islam, Rabia
Cho, Y-D
Ryu, K-M
Shin, H-R
Woo, K-M
Baek, J-H
Ryoo, H-M
Journal name Journal of cellular physiology
Volume number 230
Issue number 3
Start page 640
End page 647
Total pages 8
Publisher Wiley
Place of publication Chichester, Eng.
Publication date 2015-03
ISSN 1097-4652
Keyword(s) Animals
Bone Morphogenetic Protein 2
Cell Differentiation
Gene Expression Regulation, Developmental
NIMA-Interacting Peptidylprolyl Isomerase
Peptidylprolyl Isomerase
Protein Binding
Signal Transduction
Smad1 Protein
Transcriptional Activation
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Summary Pin1 is a peptidyl prolyl cis-trans isomerase that specifically binds to the phosphoserine-proline or phosphothreonine-proline motifs of numerous proteins. Previously, we reported that Pin1 deficiency resulted in defects in osteoblast differentiation during early bone development. In this study, we found that adult Pin1-deficient mice developed osteoporotic phenotypes compared to age-matched controls. Since BMP2 stored in the bone matrix plays a critical role in adult bone maintenance, we suspected that BMP R-Smads (Smad1 and Smad5) could be critical targets for Pin1 action. Pin1 specifically binds to the phosphorylated linker region of Smad1, which leads to structural modification and stabilization of the Smad1 protein. In this process, Pin1-mediated conformational modification of Smad1 directly suppresses the Smurf1 interaction with Smad1, thereby promoting sustained activation of the Smad1 molecule. Our data demonstrate that post-phosphorylational prolyl isomerization of Smad1 is a converging signal to stabilize the Smad1 molecule against the ubiquitination process mediated by Smurf1. Therefore, Pin1 is a critical molecular switch in the determination of Smad1 fate, opposing the death signal transmitted to the Smad1 linker region by phosphorylation cascades after its nuclear localization and transcriptional activation. Thus, Pin1 could be developed as a major therapeutic target in many skeletal diseases.
Language eng
DOI 10.1002/jcp.24787
Field of Research 1116 Medical Physiology
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, WILEY PERIODICALS, INC
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