title: Endoplasmic reticulum protein GliPR1 regulates G protein signaling and the cell cycle and is overexpressed in AML.
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.
authors.affiliation: Department of Hematology/Oncology and Infectious Diseases, J.W. Goethe University Hospital, D‑60590 Frankfurt/Main, Germany.
authors.forename: Gianni
authors.initials: G
authors.lastname: Capalbo
authors.forename: Thea
authors.initials: T
authors.lastname: Mueller-Kuller
authors.forename: Steffen
authors.initials: S
authors.lastname: Koschmieder
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Klein
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Urban J
authors.initials: UJ
authors.lastname: Scheuring
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle; D049109:Cell Proliferation; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D020555:GTP-Binding Protein Regulators / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*
chemical_list: C094538:GLIPR1 protein, human; D020555:GTP-Binding Protein Regulators; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins