Mostrar el registro sencillo del ítem
dc.contributor.author
Norris Mullins, Brianna
dc.contributor.author
VanderKolk, Kaitlin
dc.contributor.author
Vacchina, Paola

dc.contributor.author
Joyce, Michelle V.
dc.contributor.author
Morales, Miguel A.
dc.date.available
2017-12-20T13:44:49Z
dc.date.issued
2014-01
dc.identifier.citation
Morales, Miguel A.; Joyce, Michelle V.; Vacchina, Paola; VanderKolk, Kaitlin; Norris Mullins, Brianna; LmaPA2G4, a Homolog of Human Ebp1, Is an Essential Gene and Inhibits Cell Proliferation in L. major; Public Library of Science; Neglected Tropical Diseases; 8; 1; 1-2014
dc.identifier.issn
1935-2735
dc.identifier.uri
http://hdl.handle.net/11336/31091
dc.description.abstract
We have identified LmaPA2G4, a homolog of the human proliferation-associated 2G4 protein (also termed Ebp1), in aphosphoproteomic screening. Multiple sequence alignment and cluster analysis revealed that LmaPA2G4 is a non-peptidasemember of the M24 family of metallopeptidases. This pseudoenzyme is structurally related to methionine aminopeptidases. Anull mutant system based on negative selection allowed us to demonstrate that LmaPA2G4 is an essential gene inLeishmaniamajor. Over-expression of LmaPA2G4 did not alter cell morphology or the ability to differentiate into metacyclic and amastigotestages. Interestingly, the over-expression affected cell proliferation and virulence in mouse footpad analysis. LmaPA2G4 binds asynthetic double-stranded RNA polyriboinosinic polyribocytidylic acid [poly(I:C)] as shown in an electrophoretic mobility shiftassay (EMSA). Quantitative proteomics revealed that the over-expression of LmaPA2G4 led to accumulation of factors involved intranslation initiation and elongation. Significantly, we found a strong reduction ofde novoprotein biosynthesis in transgenicparasites using a non-radioactive metabolic labeling assay. In conclusion, LmaPA2G4 is an essential gene and is potentiallyimplicated in fundamental biological mechanisms, such as translation, making it an attractive target for therapeutic intervention.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science

dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Leishmania
dc.subject
Comparative Proteomics
dc.subject.classification
Otras Ciencias Biológicas

dc.subject.classification
Ciencias Biológicas

dc.subject.classification
CIENCIAS NATURALES Y EXACTAS

dc.title
LmaPA2G4, a Homolog of Human Ebp1, Is an Essential Gene and Inhibits Cell Proliferation in L. major
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-12-04T19:16:35Z
dc.journal.volume
8
dc.journal.number
1
dc.journal.pais
Estados Unidos

dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Norris Mullins, Brianna. University Of Notre Dame-Indiana; Estados Unidos
dc.description.fil
Fil: VanderKolk, Kaitlin. University Of Notre Dame-Indiana; Estados Unidos
dc.description.fil
Fil: Vacchina, Paola. University Of Notre Dame-Indiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Joyce, Michelle V.. University Of Notre Dame-Indiana; Estados Unidos
dc.description.fil
Fil: Morales, Miguel A.. University Of Notre Dame-Indiana; Estados Unidos
dc.journal.title
Neglected Tropical Diseases

dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pntd.0002646.g008
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosntds/article/figure?id=10.1371/journal.pntd.0002646.g008
Archivos asociados