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Biomolecules 2017, 7(3), 55; doi:10.3390/biom7030055

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

1
Institute of Anatomy and Cell Biology, Justus-Liebig-University, 35392 Giessen, Germany
2
Institute of Pathology, Justus-Liebig-University, 35392 Giessen, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Jürg Bähler
Received: 18 April 2017 / Revised: 14 July 2017 / Accepted: 19 July 2017 / Published: 21 July 2017
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Abstract

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. View Full-Text
Keywords: PTPIP51; LDC-3; protein–protein interaction; protein complex; scaffold protein PTPIP51; LDC-3; protein–protein interaction; protein complex; scaffold protein
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MDPI and ACS Style

Brobeil, A.; Chehab, R.; Dietel, E.; Gattenlöhner, S.; Wimmer, M. Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling. Biomolecules 2017, 7, 55.

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