title: Menin is a regulator of the stress response in Drosophila melanogaster.
abstract: Menin, the product of the multiple endocrine neoplasia type I gene, has been implicated in several biological processes, including the control of gene expression and apoptosis, the modulation of mitogen-activated protein kinase pathways, and DNA damage sensing or repair. In this study, we have investigated the function of menin in the model organism Drosophila melanogaster. We show that Drosophila lines overexpressing menin or an RNA interference for this gene develop normally but are impaired in their response to several stresses, including heat shock, hypoxia, hyperosmolarity and oxidative stress. In the embryo subjected to heat shock, this impairment was characterized by a high degree of developmental arrest and lethality. The overexpression of menin enhanced the expression of HSP70 in embryos and interfered with its down-regulation during recovery at the normal temperature. In contrast, the inhibition of menin with RNA interference reduced the induction of HSP70 and blocked the activation of HSP23 upon heat shock, Menin was recruited to the Hsp70 promoter upon heat shock and menin overexpression stimulated the activity of this promoter in embryos. A 70-kDa inducible form of menin was expressed in response to heat shock, indicating that menin is also regulated in conditions of stress. The induction of HSP70 and HSP23 was markedly reduced or absent in mutant embryos harboring a deletion of the menin gene. These embryos, which did not express the heat shock-inducible form of menin, were also hypersensitive to various conditions of stress. These results suggest a novel role for menin in the control of the stress response and in processes associated with the maintenance of protein integrity.
authors.affiliation: Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: Maria
authors.initials: M
authors.lastname: Papaconstantinou
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Hendrik Nikolaas
authors.initials: HN
authors.lastname: Pretorius
authors.forename: Nishi
authors.initials: N
authors.lastname: Singh
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gianfelice
authors.forename: Robert M
authors.initials: RM
authors.lastname: Tanguay
authors.forename: Ana Regina
authors.initials: AR
authors.lastname: Campos
authors.forename: Pierre-André
authors.initials: PA
authors.lastname: Bédard
mesh_terms: D000165:Acridine Orange / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000502:physiology*; D004331:Drosophila melanogaster; D005456:Fluorescent Dyes / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006358:Hot Temperature; D000860:Hypoxia; D007150:Immunohistochemistry; D008938:Mitosis; D009154:Mutation; D018384:Oxidative Stress; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000502:physiology*; D034622:RNA Interference; D013696:Temperature; D013997:Time Factors; D014132:Trachea / Q000378:metabolism / Q000473:pathology; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D005456:Fluorescent Dyes; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C105998:Hsp23 protein, Drosophila; C105373:MEN1 protein, human; C499857:Mnn1 protein, Drosophila; D011518:Proto-Oncogene Proteins; D004247:DNA; D001616:beta-Galactosidase; D000165:Acridine Orange