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Structural and cellular mechanisms of peptidyl-prolyl isomerase Pin1-mediated enhancement of Tissue Factor gene expression, protein half-life, and pro-coagulant activity

Tissue Factor is a cell-surface glycoprotein expressed in various cells of the vasculature and is the principal regulator of the blood coagulation cascade and hemostasis. Notably, aberrant expression of Tissue Factor is associated with cardiovascular pathologies such as atherosclerosis and thrombosi...

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Autores principales: Kurakula, Kondababu, Koenis, Duco S., Herzik, Mark A., Liu, Yanyun, Craft, John W., van Loenen, Pieter B., Vos, Mariska, Tran, M. Khang, Versteeg, Henri H., Goumans, Marie-José T.H., Ruf, Wolfram, de Vries, Carlie J.M., Şen, Mehmet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ferrata Storti Foundation 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058786/
https://www.ncbi.nlm.nih.gov/pubmed/29545340
http://dx.doi.org/10.3324/haematol.2017.183087
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author Kurakula, Kondababu
Koenis, Duco S.
Herzik, Mark A.
Liu, Yanyun
Craft, John W.
van Loenen, Pieter B.
Vos, Mariska
Tran, M. Khang
Versteeg, Henri H.
Goumans, Marie-José T.H.
Ruf, Wolfram
de Vries, Carlie J.M.
Şen, Mehmet
author_facet Kurakula, Kondababu
Koenis, Duco S.
Herzik, Mark A.
Liu, Yanyun
Craft, John W.
van Loenen, Pieter B.
Vos, Mariska
Tran, M. Khang
Versteeg, Henri H.
Goumans, Marie-José T.H.
Ruf, Wolfram
de Vries, Carlie J.M.
Şen, Mehmet
author_sort Kurakula, Kondababu
collection PubMed
description Tissue Factor is a cell-surface glycoprotein expressed in various cells of the vasculature and is the principal regulator of the blood coagulation cascade and hemostasis. Notably, aberrant expression of Tissue Factor is associated with cardiovascular pathologies such as atherosclerosis and thrombosis. Here, we sought to identify factors that regulate Tissue Factor gene expression and activity. Tissue Factor gene expression is regulated by various transcription factors, including activating protein-1 and nuclear factor-κ B. The peptidyl-prolyl isomerase Pin1 is known to modulate the activity of these two transcription factors, and we now show that Pin1 augments Tissue Factor gene expression in both vascular smooth muscle cells and activated endothelial cells via activating protein-1 and nuclear factor-κ B signaling. Furthermore, the cytoplasmic domain of Tissue Factor contains a well-conserved phospho-Ser258-Pro259 amino-acid motif recognized by Pin1. Using co-immunoprecipitation and solution nuclear magnetic resonance spectroscopy, we show that the WW-domain of Pin1 directly binds the cytoplasmic domain of Tissue Factor. This interaction occurs via the phospho-Ser258-Pro259 sequence in the Tissue Factor cytoplasmic domain and results in increased protein half-life and pro-coagulant activity. Taken together, our results establish Pin1 as an upstream regulator of Tissue Factor-mediated coagulation, thereby opening up new avenues for research into the use of specific Pin1 inhibitors for the treatment of diseases characterized by pathological coagulation, such as thrombosis and atherosclerosis.
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spelling pubmed-60587862018-08-02 Structural and cellular mechanisms of peptidyl-prolyl isomerase Pin1-mediated enhancement of Tissue Factor gene expression, protein half-life, and pro-coagulant activity Kurakula, Kondababu Koenis, Duco S. Herzik, Mark A. Liu, Yanyun Craft, John W. van Loenen, Pieter B. Vos, Mariska Tran, M. Khang Versteeg, Henri H. Goumans, Marie-José T.H. Ruf, Wolfram de Vries, Carlie J.M. Şen, Mehmet Haematologica Article Tissue Factor is a cell-surface glycoprotein expressed in various cells of the vasculature and is the principal regulator of the blood coagulation cascade and hemostasis. Notably, aberrant expression of Tissue Factor is associated with cardiovascular pathologies such as atherosclerosis and thrombosis. Here, we sought to identify factors that regulate Tissue Factor gene expression and activity. Tissue Factor gene expression is regulated by various transcription factors, including activating protein-1 and nuclear factor-κ B. The peptidyl-prolyl isomerase Pin1 is known to modulate the activity of these two transcription factors, and we now show that Pin1 augments Tissue Factor gene expression in both vascular smooth muscle cells and activated endothelial cells via activating protein-1 and nuclear factor-κ B signaling. Furthermore, the cytoplasmic domain of Tissue Factor contains a well-conserved phospho-Ser258-Pro259 amino-acid motif recognized by Pin1. Using co-immunoprecipitation and solution nuclear magnetic resonance spectroscopy, we show that the WW-domain of Pin1 directly binds the cytoplasmic domain of Tissue Factor. This interaction occurs via the phospho-Ser258-Pro259 sequence in the Tissue Factor cytoplasmic domain and results in increased protein half-life and pro-coagulant activity. Taken together, our results establish Pin1 as an upstream regulator of Tissue Factor-mediated coagulation, thereby opening up new avenues for research into the use of specific Pin1 inhibitors for the treatment of diseases characterized by pathological coagulation, such as thrombosis and atherosclerosis. Ferrata Storti Foundation 2018-06 /pmc/articles/PMC6058786/ /pubmed/29545340 http://dx.doi.org/10.3324/haematol.2017.183087 Text en Copyright © 2018 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.
spellingShingle Article
Kurakula, Kondababu
Koenis, Duco S.
Herzik, Mark A.
Liu, Yanyun
Craft, John W.
van Loenen, Pieter B.
Vos, Mariska
Tran, M. Khang
Versteeg, Henri H.
Goumans, Marie-José T.H.
Ruf, Wolfram
de Vries, Carlie J.M.
Şen, Mehmet
Structural and cellular mechanisms of peptidyl-prolyl isomerase Pin1-mediated enhancement of Tissue Factor gene expression, protein half-life, and pro-coagulant activity
title Structural and cellular mechanisms of peptidyl-prolyl isomerase Pin1-mediated enhancement of Tissue Factor gene expression, protein half-life, and pro-coagulant activity
title_full Structural and cellular mechanisms of peptidyl-prolyl isomerase Pin1-mediated enhancement of Tissue Factor gene expression, protein half-life, and pro-coagulant activity
title_fullStr Structural and cellular mechanisms of peptidyl-prolyl isomerase Pin1-mediated enhancement of Tissue Factor gene expression, protein half-life, and pro-coagulant activity
title_full_unstemmed Structural and cellular mechanisms of peptidyl-prolyl isomerase Pin1-mediated enhancement of Tissue Factor gene expression, protein half-life, and pro-coagulant activity
title_short Structural and cellular mechanisms of peptidyl-prolyl isomerase Pin1-mediated enhancement of Tissue Factor gene expression, protein half-life, and pro-coagulant activity
title_sort structural and cellular mechanisms of peptidyl-prolyl isomerase pin1-mediated enhancement of tissue factor gene expression, protein half-life, and pro-coagulant activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058786/
https://www.ncbi.nlm.nih.gov/pubmed/29545340
http://dx.doi.org/10.3324/haematol.2017.183087
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