title: Androgen-inducible gene 1 increases the ER Ca(2+) content and cell death susceptibility against oxidative stress.
abstract: Androgen-induced gene 1 (AIG1) is a transmembrane protein implicated with survival (its expression level was shown to correlate with the survival of patients suffering from hepatocellular carcinoma) and Ca(2+) signaling (over-expression of AIG1 increased transcription mediated by the Ca(2+)-dependent nuclear factor of activated T cells). We aimed to shed light on this less-studied protein and investigated its tissue expression, genomic organization, intracellular localization and membrane topology as well as its effects on cell death susceptibility and the Ca(2+) content of the endoplasmic reticulum. Immunoblotting of mouse tissues demonstrated highest expression of AIG1 in the liver, lung and heart. AIG1 has a complex genomic organization and expresses several splice variants in a tissue-dependent manner. Analyzing the topology of AIG1 in the ER membrane using a protease-protection assay suggested that AIG has five transmembrane domains with a luminal N- and cytosolic C-terminus and a hydrophobic stretch between the third and fourth membrane domain that does not cross the membrane. AIG1 over-expression slightly increased susceptibility to oxidative stress, which correlated with an increased ER Ca(2+) concentration in two different cell lines. Together, these results indicate that AIG1 plays a role in the control of the intracellular Ca(2+) concentration and cell death susceptibility.
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)) and Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Nickel
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)) and Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Cleven
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)) and Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Vitalij
authors.initials: V
authors.lastname: Enders
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)) and Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Lisak
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)) and Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Schneider
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)) and Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. Electronic address: axel.methner@gmail.com.
authors.forename: Axel
authors.initials: A
authors.lastname: Methner
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D018384:Oxidative Stress; D000072417:Protein Domains; D012727:Sex Characteristics
chemical_list: C000613195:AIG1 protein, mouse; D008565:Membrane Proteins; D002118:Calcium
keywords: AIG1; Ca(2+); Endoplasmic reticulum stress; Membrane proteins; Oxidative stress