| Author | Melo Neto, Osvaldo P. de | |
| Author | Lima, Tamara D. C. da Costa | |
| Author | Merlo, Kleison C. | |
| Author | Romão, Tatiany P. | |
| Author | Rocha, Pollyanna O. | |
| Author | Assis, Ludmila A. | |
| Author | Nascimento, Larissa M. | |
| Author | Xavier, Camila C. | |
| Author | Rezende, Antonio M. | |
| Author | Reis, Christian R. S. | |
| Author | Papadopoulou, Barbara | |
| Access date | 2019-05-09T13:25:44Z | |
| Available date | 2019-05-09T13:25:44Z | |
| Document date | 2018 | |
| Citation | MELO 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. | pt_BR |
| ISSN | 1555-8584 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/33013 | |
| Sponsorship | CNPq - 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. | pt_BR |
| Language | eng | pt_BR |
| Rights | restricted access | pt_BR |
| Title | Phosphorylation and interactions associated with the control of the Leishmania Poly-A Binding Protein 1 (PABP1) function during translation initiation | pt_BR |
| Type | Article | |
| DOI | 10.1080/15476286.2018.1445958 | pt_BR |
| Abstract | The 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. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | UNITA. Centro Universitário Tabosa de Almeida. Caruaru, Pernambuco, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | Laval University. CHU de Quebec Research. Center and Department of Microbiology-Infectious Disease and Immunology. Canadá. | pt_BR |
| Subject | Leishmania | pt_BR |
| Subject | Translation | pt_BR |
| Subject | Phosphorylation | pt_BR |
| Subject | Proteinprotein interaction | pt_BR |
| Subject | Translation initiation factor | pt_BR |
| Subject | Polyadenylate-binding protein | pt_BR |
| DeCS | Motivos de Aminoácidos | pt_BR |
| DeCS | Leishmania infantum / genética | pt_BR |
| DeCS | Leishmania infantum / metabolismo | pt_BR |
| DeCS | Iniciação da Cadeia Peptídica, Translacional / fisiologia | pt_BR |
| DeCS | Fosforilação / fisiologia | pt_BR |
| DeCS | Proteínas de Ligação Poli (A) / genética | pt_BR |
| DeCS | Proteínas de Ligação Poli (A) / metabolismo | pt_BR |
| DeCS | Proteínas Protozoárias / genética | pt_BR |
| DeCS | Proteínas Protozoárias / metabolismo | pt_BR |
| e-ISSN | 10.1080/15476286.2018.1445958 | |
| Embargo date | 2050-01-01 | |
