title: Sumoylation of eIF4A2 affects stress granule formation.
abstract: Regulation of protein synthesis is crucial for cells to maintain viability and to prevent unscheduled proliferation that could lead to tumorigenesis. Exposure to stress results in stalling of translation, with many translation initiation factors, ribosomal subunits and mRNAs being sequestered into stress granules or P bodies. This allows the re-programming of the translation machinery. Many aspects of translation are regulated by post-translational modification. Several proteomic screens have identified translation initiation factors as targets for sumoylation, although in many cases the role of this modification has not been determined. We show here that eIF4A2 is modified by SUMO, with sumoylation occurring on a single residue (K226). We demonstrate that sumoylation of eIF4A2 is modestly increased in response to arsenite and ionising radiation, but decreases in response to heat shock or hippuristanol. In arsenite-treated cells, but not in hippuristanol-treated cells, eIF4A2 is recruited to stress granules, suggesting sumoylation of eIF4A2 correlates with its recruitment to stress granules. Furthermore, we demonstrate that the inability to sumoylate eIF4A2 results in impaired stress granule formation, indicating a new role for sumoylation in the stress response.
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Jirapas
authors.initials: J
authors.lastname: Jongjitwimol
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Baldock
authors.affiliation: Department of Biochemistry and Biomedical Science, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Morley
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK f.z.watts@sussex.ac.uk.
authors.forename: Felicity Z
authors.identifier: 0000-0002-4956-3504
authors.initials: FZ
authors.lastname: Watts
mesh_terms: D000595:Amino Acid Sequence; D018053:Arsenites / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D039601:Eukaryotic Initiation Factor-4A / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D018869:Heat-Shock Response / Q000187:drug effects; D006801:Humans; D009154:Mutation / Q000235:genetics; D011839:Radiation, Ionizing; D013261:Sterols / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects / Q000528:radiation effects; D058207:Sumoylation / Q000187:drug effects / Q000528:radiation effects
chemical_list: D018053:Arsenites; D013261:Sterols; C510125:hippuristanol; D039601:Eukaryotic Initiation Factor-4A; C015001:arsenite
keywords: Arsenite; Heat shock; Hippuristanol; Ionising radiation; Protein synthesis; SUMO; Translation