title: A novel 4EHP-GIGYF2 translational repressor complex is essential for mammalian development.
abstract: The binding of the eukaryotic initiation factor 4E (eIF4E) to the mRNA 5' cap structure is a rate-limiting step in mRNA translation initiation. eIF4E promotes ribosome recruitment to the mRNA. In Drosophila, the eIF4E homologous protein (d4EHP) forms a complex with binding partners to suppress the translation of distinct mRNAs by competing with eIF4E for binding the 5' cap structure. This repression mechanism is essential for the asymmetric distribution of proteins and normal embryonic development in Drosophila. In contrast, the physiological role of the mammalian 4EHP (m4EHP) was not known. In this study, we have identified the Grb10-interacting GYF protein 2 (GIGYF2) and the zinc finger protein 598 (ZNF598) as components of the m4EHP complex. GIGYF2 directly interacts with m4EHP, and this interaction is required for stabilization of both proteins. Disruption of the m4EHP-GIGYF2 complex leads to increased translation and perinatal lethality in mice. We propose a model by which the m4EHP-GIGYF2 complex represses translation of a subset of mRNAs during embryonic development, as was previously reported for d4EHP.
authors: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montréal, Quebec, Canada.
authors: Masahiro
authors: M
authors: Morita
authors: Lian Wee
authors: LW
authors: Ler
authors: Marc R
authors: MR
authors: Fabian
authors: Nadeem
authors: N
authors: Siddiqui
authors: Michael
authors: M
authors: Mullin
authors: Valerie C
authors: VC
authors: Henderson
authors: Tommy
authors: T
authors: Alain
authors: Bruno D
authors: BD
authors: Fonseca
authors: Galina
authors: G
authors: Karashchuk
authors: Christopher F
authors: CF
authors: Bennett
authors: Tomohiro
authors: T
authors: Kabuta
authors: Shinji
authors: S
authors: Higashi
authors: Ola
authors: O
authors: Larsson
authors: Ivan
authors: I
authors: Topisirovic
authors: Robert J
authors: RJ
authors: Smith
authors: Anne-Claude
authors: AC
authors: Gingras
authors: Nahum
authors: N
authors: Sonenberg
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D014176:Protein Biosynthesis; D054730:Protein Interaction Domains and Motifs; D060066:Protein Interaction Maps
chemical_list: D002352:Carrier Proteins; D039561:Eukaryotic Initiation Factor-4E; C478016:GIGYF2 protein, human; C547020:GIGYF2 protein, mouse; C575874:ZNF598 protein, human