Phosphorylation and interactions associated with the control of the Leishmania Poly-A Binding Protein 1 (PABP1) function during translation initiation

dc.creatorMelo Neto, Osvaldo P. de
dc.creatorLima, Tamara D. C. da Costa
dc.creatorMerlo, Kleison C.
dc.creatorRomão, Tatiany P.
dc.creatorRocha, Pollyanna O.
dc.creatorAssis, Ludmila A.
dc.creatorNascimento, Larissa M.
dc.creatorXavier, Camila C.
dc.creatorRezende, Antonio M.
dc.creatorReis, Christian R. S.
dc.creatorPapadopoulou, Barbara
dc.date2019-05-09T13:25:44Z
dc.date2019-05-09T13:25:44Z
dc.date2018
dc.date.accessioned2023-09-26T22:59:37Z
dc.date.available2023-09-26T22:59:37Z
dc.identifierMELO NETO, Osvaldo P. de et al. Phosphorylation and Interactions Associated with the Control of the Leishmania Poly-A Binding Protein 1 (PABP1) Function during Translation Initiation. RNA Biology, v. 15, n. 6, p. 739–755, 2018.
dc.identifier1555-8584
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/33013
dc.identifier10.1080/15476286.2018.1445958
dc.identifier10.1080/15476286.2018.1445958
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8885622
dc.descriptionCNPq - Brazil, 480899/2013-4 Capes - Brazil, 23038.007656/2011-92 CNPq - Brazil, 313934/2013-4 Facepe - Brazil, APQ-0239-2.02/12 MDEIE - Canada, PSR-SIIRI-439 NSERC - Canada, 418444 Government of Canada j Canadian Institutes of Health Research (CIHR), MOP-12182.
dc.descriptionThe Poly-A Binding Protein (PABP) is a conserved eukaryotic polypeptide involved in many aspects of mRNA metabolism. During translation initiation, PABP interacts with the translation initiation complex eIF4F and enhances the translation of polyadenylated mRNAs. Schematically, most PABPs can be divided into an N-terminal RNA-binding region, a non-conserved linker segment and the C-terminal MLLE domain. In pathogenic Leishmania protozoans, three PABP homologues have been identified, with the first one (PABP1) targeted by phosphorylation and shown to co-immunoprecipitate with an eIF4F-like complex (EIF4E4/EIF4G3) implicated in translation initiation. Here, PABP1 phosphorylation was shown to be linked to logarithmic cell growth, reminiscent of EIF4E4 phosphorylation, and coincides with polysomal association. Phosphorylation targets multiple serine-proline (SP) or threonine-proline (TP) residues within the PABP1 linker region. This is an essential protein, but phosphorylation is not needed for its association with polysomes or cell viability. Mutations which do impair PABP1 polysomal association and are required for viability do not prevent phosphorylation, although further mutations lead to a presumed inactive protein largely lacking phosphorylated isoforms. Co-immunoprecipitation experiments were carried out to investigate PABP1 function further, identifying several novel protein partners and the EIF4E4/EIF4G3 complex, but no other eIF4F-like complex or subunit. A novel, direct interaction between PABP1 and EIF4E4 was also investigated and found to be mediated by the PABP1 MLLE binding to PABP Interacting Motifs (PAM2) within the EIF4E4 N-terminus. The results shown here are consistent with phosphorylation of PABP1 being part of a novel pathway controlling its function and possibly translation in Leishmania.
dc.description2050-01-01
dc.formatapplication/pdf
dc.languageeng
dc.rightsrestricted access
dc.subjectLeishmania
dc.subjectTranslation
dc.subjectPhosphorylation
dc.subjectProteinprotein interaction
dc.subjectTranslation initiation factor
dc.subjectPolyadenylate-binding protein
dc.subjectMotivos de Aminoácidos
dc.subjectLeishmania infantum / genética
dc.subjectLeishmania infantum / metabolismo
dc.subjectIniciação da Cadeia Peptídica, Translacional / fisiologia
dc.subjectFosforilação / fisiologia
dc.subjectProteínas de Ligação Poli (A) / genética
dc.subjectProteínas de Ligação Poli (A) / metabolismo
dc.subjectProteínas Protozoárias / genética
dc.subjectProteínas Protozoárias / metabolismo
dc.titlePhosphorylation and interactions associated with the control of the Leishmania Poly-A Binding Protein 1 (PABP1) function during translation initiation
dc.typeArticle


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