Endoplasmic reticulum protein GliPR1 regulates G protein signaling and the cell cycle and is overexpressed in AML

Capalbo,Gianni; Mueller-Kuller,Thea; Koschmieder,Steffen; Klein,Hans-Ulrich; Ottmann,Oliver  G.; Hoelzer,Dieter; Scheuring,Urban   J.

doi:10.3892/or.2013.2716

Endoplasmic reticulum protein GliPR1 regulates G protein signaling and the cell cycle and is overexpressed in AML

Authors:
- Gianni Capalbo
- Thea Mueller-Kuller
- Steffen Koschmieder
- Hans-Ulrich Klein
- Oliver G. Ottmann
- Dieter Hoelzer
- Urban J. Scheuring
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Affiliations: Department of Hematology/Oncology and Infectious Diseases, J.W. Goethe University Hospital, D‑60590 Frankfurt/Main, Germany, Department of Oncology, Hematology, and Stem Cell Transplantation, University Medical Center of Aachen, D‑52074 Aachen, Germany, Institute of Medical Informatics, University of Münster, D‑48149 Münster, Germany
Published online on: September 4, 2013 https://doi.org/10.3892/or.2013.2716
Pages: 2254-2262

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Abstract

Glioma pathogenesis‑related protein 1 (GliPR1) is a pleiotropic protein involved in cell proliferation, tumor growth and apoptosis. The aim of the present study was to further characterize GliPR1 in regard to its subcellular localization and its overall effect on cellular gene expression. Knockdown of GliPR1 and Affymetrix microarray mRNA expression analysis revealed 262 GliPR1‑dependent differentially expressed genes, of which 40 were induced and 222 were suppressed. Differentially expressed genes were overrepresented in five Gene Ontology categories: G protein signaling pathways, regulation of cyclin‑dependent protein kinase activity, ER to Golgi vesicle-mediated transport, axon guidance and dephosphorylation. GliPR1-EGFP fusion protein co‑localized with the endoplasmic reticulum (ER) or with cytoplasmic vesicles as demonstrated by confocal microscopy. GliPR1 expression was found to be significantly increased in acute myeloid leukemia (AML) bone marrow samples, while markedly reduced in acute lymphoblastic leukemia, unchanged in myelodysplastic syndrome and slightly decreased in chronic lymphocytic leukemia as well as in chronic myelocytic leukemia (CML) when compared to normal samples. GliPR1 was localized and involved in the ER secretory protein pathway. GliPR1 affects G protein signaling and cell cycle regulation. Based on the observed overexpression in AML samples, GliPR1 should be further explored as a potential target for AML.

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