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Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling

Protein–protein interactions play a pivotal role in normal cellular functions as well as in carcinogenesis. The protein–protein interactions form functional clusters during signal transduction. To elucidate the fine calibration of the protein–protein interactions of protein tyrosine phosphatase inte...

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Autores principales: Brobeil, Alexander, Chehab, Rajaa, Dietel, Eric, Gattenlöhner, Stefan, Wimmer, Monika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618236/
https://www.ncbi.nlm.nih.gov/pubmed/28754031
http://dx.doi.org/10.3390/biom7030055
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author Brobeil, Alexander
Chehab, Rajaa
Dietel, Eric
Gattenlöhner, Stefan
Wimmer, Monika
author_facet Brobeil, Alexander
Chehab, Rajaa
Dietel, Eric
Gattenlöhner, Stefan
Wimmer, Monika
author_sort Brobeil, Alexander
collection PubMed
description Protein–protein interactions play a pivotal role in normal cellular functions as well as in carcinogenesis. The protein–protein interactions form functional clusters during signal transduction. To elucidate the fine calibration of the protein–protein interactions of protein tyrosine phosphatase interacting protein 51 (PTPIP51) a small molecule drug, namely LDC-3, directly targeting PTPIP51 is now available. Therefore, LDC-3 allows for the studying of the regulation of the endogenous interactome by modulating PTPIP51 binding capacity. Small interfering ribonucleic acid (siRNA) experiments show that the modification in PTPIP51 binding capacity is induced by LDC-3. Application of LDC-3 annuls the known regulatory phosphorylation mechanisms for PTPIP51 and consequently, significantly alters the assembly of the PTPIP51 associated protein complexes. The treatment of human keratinocytes (HaCaT cells) with LDC-3 induces an altered protein–protein interaction profile of the endogenous interactome of PTPIP51. In addition, LDC-3 stabilizes PTPIP51 within a mitogen activated protein kinase (MAPK) complex composed of Raf-1 and the scaffold protein 14-3-3, independent of the phosphorylation status of PTPIP51. Of note, under LDC-3 treatment the regulatory function of the PTP1B on PTPIP51 fails to impact the PTPIP51 interaction characteristics, as reported for the HaCaT cell line. In summary, LDC-3 gives the unique opportunity to directly modulate PTPIP51 in malignant cells, thus targeting potential dysregulated signal transduction pathways such as the MAPK cascade. The provided data give critical insights in the therapeutic potential of PTPIP51 protein interactions and thus are basic for possible targeted therapy regimens.
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spelling pubmed-56182362017-09-29 Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling Brobeil, Alexander Chehab, Rajaa Dietel, Eric Gattenlöhner, Stefan Wimmer, Monika Biomolecules Article Protein–protein interactions play a pivotal role in normal cellular functions as well as in carcinogenesis. The protein–protein interactions form functional clusters during signal transduction. To elucidate the fine calibration of the protein–protein interactions of protein tyrosine phosphatase interacting protein 51 (PTPIP51) a small molecule drug, namely LDC-3, directly targeting PTPIP51 is now available. Therefore, LDC-3 allows for the studying of the regulation of the endogenous interactome by modulating PTPIP51 binding capacity. Small interfering ribonucleic acid (siRNA) experiments show that the modification in PTPIP51 binding capacity is induced by LDC-3. Application of LDC-3 annuls the known regulatory phosphorylation mechanisms for PTPIP51 and consequently, significantly alters the assembly of the PTPIP51 associated protein complexes. The treatment of human keratinocytes (HaCaT cells) with LDC-3 induces an altered protein–protein interaction profile of the endogenous interactome of PTPIP51. In addition, LDC-3 stabilizes PTPIP51 within a mitogen activated protein kinase (MAPK) complex composed of Raf-1 and the scaffold protein 14-3-3, independent of the phosphorylation status of PTPIP51. Of note, under LDC-3 treatment the regulatory function of the PTP1B on PTPIP51 fails to impact the PTPIP51 interaction characteristics, as reported for the HaCaT cell line. In summary, LDC-3 gives the unique opportunity to directly modulate PTPIP51 in malignant cells, thus targeting potential dysregulated signal transduction pathways such as the MAPK cascade. The provided data give critical insights in the therapeutic potential of PTPIP51 protein interactions and thus are basic for possible targeted therapy regimens. MDPI 2017-07-21 /pmc/articles/PMC5618236/ /pubmed/28754031 http://dx.doi.org/10.3390/biom7030055 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brobeil, Alexander
Chehab, Rajaa
Dietel, Eric
Gattenlöhner, Stefan
Wimmer, Monika
Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling
title Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling
title_full Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling
title_fullStr Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling
title_full_unstemmed Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling
title_short Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling
title_sort altered protein interactions of the endogenous interactome of ptpip51 towards mapk signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618236/
https://www.ncbi.nlm.nih.gov/pubmed/28754031
http://dx.doi.org/10.3390/biom7030055
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