Next Article in Journal
Cell Cycle Regulation by Ca2+-Activated K+ (BK) Channels Modulators in SH-SY5Y Neuroblastoma Cells
Next Article in Special Issue
Radiation Sensitization of Basal Cell and Head and Neck Squamous Cell Carcinoma by the Hedgehog Pathway Inhibitor Vismodegib
Previous Article in Journal
Functional Characterization of An Allene Oxide Synthase Involved in Biosynthesis of Jasmonic Acid and Its Influence on Metabolite Profiles and Ethylene Formation in Tea (Camellia sinensis) Flowers
Previous Article in Special Issue
Application of Fluorescence Lifetime Imaging Microscopy of DNA Binding Dyes to Assess Radiation-Induced Chromatin Compaction Changes
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(8), 2441; https://doi.org/10.3390/ijms19082441

Stress-Induced Phosphorylation of Nuclear YB-1 Depends on Nuclear Trafficking of p90 Ribosomal S6 Kinase

1
Division of Radiobiology & Molecular Environmental Research, Department of Radiation Oncology, University of Tuebingen, Tuebingen, Germany
2
German Consortium for Translational Cancer Research (DKTK), Partner Site Tuebingen and German Cancer Research Center (DKFZ), Heidelberg, Germany
3
Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany
4
German Consortium for Translational Cancer Research (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Received: 23 July 2018 / Revised: 14 August 2018 / Accepted: 17 August 2018 / Published: 18 August 2018
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research)
Full-Text   |   PDF [1833 KB, uploaded 18 August 2018]   |  

Abstract

Ionizing radiation (IR) and epidermal growth factor (EGF) stimulate Y-box binding protein-1 (YB-1) phosphorylation at Ser-102 in KRAS wild-type (KRASwt) cells, whereas in KRAS mutated (KRASmut) cells, YB-1 is constitutively phosphorylated, independent of IR or EGF. YB-1 activity stimulates the repair of IR-induced DNA double-strand breaks (DSBs) in the nucleus. Thus far, the YB-1 nuclear translocation pattern after cell exposure to various cellular stressors is not clear. In the present study, we investigated the pattern of YB-1 phosphorylation and its possible translocation to the nucleus in KRASwt cells after exposure to IR, EGF treatment, and conditional expression of mutated KRAS(G12V). IR, EGF, and conditional KRAS(G12V) expression induced YB-1 phosphorylation in both the cytoplasmic and nuclear fractions of KRASwt cells. None of the stimuli induced YB-1 nuclear translocation, while p90 ribosomal s6 kinase (RSK) translocation was enhanced in KRASwt cells after any of the stimuli. EGF-induced RSK translocation to the nucleus and nuclear YB-1 phosphorylation were completely blocked by the EGF receptor kinase inhibitor erlotinib. Likewise, RSK inhibition blocked RSK nuclear translocation and nuclear YB-1 phosphorylation after irradiation and KRAS(G12V) overexpression. In summary, acute stimulation of YB-1 phosphorylation does not lead to YB-1 translocation from the cytoplasm to the nucleus. Rather, irradiation, EGF treatment, or KRAS(G12V) overexpression induces RSK activation, leading to its translocation to the nucleus, where it activates already-existing nuclear YB-1. Our novel finding illuminates the signaling pathways involved in nuclear YB-1 phosphorylation and provides a rationale for designing appropriate targeting strategies to block YB-1 in oncology as well as in radiation oncology. View Full-Text
Keywords: ionizing radiation; EGF; oncogenic KRAS; nuclear YB-1; MAPK/ERK ionizing radiation; EGF; oncogenic KRAS; nuclear YB-1; MAPK/ERK
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Tiwari, A.; Rebholz, S.; Maier, E.; Dehghan Harati, M.; Zips, D.; Sers, C.; Rodemann, H.P.; Toulany, M. Stress-Induced Phosphorylation of Nuclear YB-1 Depends on Nuclear Trafficking of p90 Ribosomal S6 Kinase. Int. J. Mol. Sci. 2018, 19, 2441.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top