PTPIP51—A New RelA-tionship with the NFκB Signaling Pathway.

Alexander Brobeil,Claudia Tag,Fabian Kämmerer,Klaus Steger,Monika Wimmer,Stefan Gattenlöhner

doi:10.3390/biom5020485

Alexander Brobeil, Claudia Tag + Show 4 more

Open Access

https://doi.org/10.3390/biom5020485

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Journal: Biomolecules	Publication Date: Apr 16, 2015
Citations: 10	License type: CC BY 4.0

Affiliation: University of Giessen

Abstract

The present study shows a new connection of protein tyrosine phosphatase interacting protein 51 (PTPIP51) to the nuclear factor κB (NFκB) signalling pathway. PTPIP51 mRNA and protein expression is regulated by RelA. If bound to the PTPIP51 promoter, RelA repress the mRNA and protein expression of PTPIP51. The parallel treatment with pyrrolidine dithiocarbamate (PDTC) reversed the suppression of PTPIP51 protein expression induced by TNFα. Using the intensity correlation analysis PTPIP51 verified a co-localization with RelA, which is also regulated by TNFα administration. Moreover, the direct interaction of PTPIP51 and RelA was established using the DuoLink proximity ligation assay. IκBα, the known inhibitor of RelA, also interacted with PTPIP51. This hints to the fact that in un-stimulated conditions PTPIP51 forms a complex with RelA and IκBα. The PTPIP51/RelA/IκBα complex is modulated by TNFα. Interestingly, the impact on the mitogen activated protein kinase pathway was negligible except in highest TNFα concentration. Here, PTPIP51 and Raf-1 interactions were slightly repressed. The newly established relationship of PTPIP51 and the NFκB signaling pathway provides the basis for a possible therapeutic impact.

Highlights

In recent studies protein tyrosine phosphatase interacting protein 51 (PTPIP51) was identified to be strongly involved in the mitogen activated kinase (MAPK) signaling [1,2]
The PTPIP51 and RelA mRNA Expression is Regulated by tumor necrosis factor alpha (TNF) Administration
In the current study we show a new relationship of PTPIP51 within the nuclear factor kappa B (NFB) signaling pathway, especially the interaction with RelA

Summary

Introduction

In recent studies PTPIP51 was identified to be strongly involved in the mitogen activated kinase (MAPK) signaling [1,2]. PTPIP51 is under control of distinct kinases and phosphatases modulating its binding capability to Raf-1 and thereby titrating the MAPK signal [1,2,3]. The protein interactions of PTPIP51 are associated with cell cycle progression and PTPIP51 plays a pivotal role during chromosome segregation [4]. De Vos and co-workers corroborated the binding of PTPIP51 to the outer layer of mitochondria, where PTPIP51 function was linked to processes in the calcium homeostasis by interacting with vesicle associated protein B (VAPB) [5]. The first functional study to characterize the cellular implications of PTPIP51 showed that PTPIP51 is linked to the apoptotic process [6].

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Discussion

Conclusion