LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major.
We have identified LmaPA2G4, a homolog of the human proliferation-associated 2G4 protein (also termed Ebp1), in a phosphoproteomic screening. Multiple sequence alignment and cluster analysis revealed that LmaPA2G4 is a non-peptidase member of the M24 family of metallopeptidases. This pseudoenzyme is...
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ftdoajarticles:oai:doaj.org/article:80f0aab94ffe4226a16d51308babe940 2023-05-15T15:07:16+02:00 LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major. Brianna Norris-Mullins Kaitlin VanderKolk Paola Vacchina Michelle V Joyce Miguel A Morales 2014-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002646 https://doaj.org/article/80f0aab94ffe4226a16d51308babe940 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3888471?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002646 https://doaj.org/article/80f0aab94ffe4226a16d51308babe940 PLoS Neglected Tropical Diseases, Vol 8, Iss 1, p e2646 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002646 2022-12-31T15:18:40Z We have identified LmaPA2G4, a homolog of the human proliferation-associated 2G4 protein (also termed Ebp1), in a phosphoproteomic screening. Multiple sequence alignment and cluster analysis revealed that LmaPA2G4 is a non-peptidase member of the M24 family of metallopeptidases. This pseudoenzyme is structurally related to methionine aminopeptidases. A null mutant system based on negative selection allowed us to demonstrate that LmaPA2G4 is an essential gene in Leishmania major. Over-expression of LmaPA2G4 did not alter cell morphology or the ability to differentiate into metacyclic and amastigote stages. Interestingly, the over-expression affected cell proliferation and virulence in mouse footpad analysis. LmaPA2G4 binds a synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid [poly(I∶C)] as shown in an electrophoretic mobility shift assay (EMSA). Quantitative proteomics revealed that the over-expression of LmaPA2G4 led to accumulation of factors involved in translation initiation and elongation. Significantly, we found a strong reduction of de novo protein biosynthesis in transgenic parasites using a non-radioactive metabolic labeling assay. In conclusion, LmaPA2G4 is an essential gene and is potentially implicated in fundamental biological mechanisms, such as translation, making it an attractive target for therapeutic intervention. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 1 e2646 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Brianna Norris-Mullins Kaitlin VanderKolk Paola Vacchina Michelle V Joyce Miguel A Morales LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
We have identified LmaPA2G4, a homolog of the human proliferation-associated 2G4 protein (also termed Ebp1), in a phosphoproteomic screening. Multiple sequence alignment and cluster analysis revealed that LmaPA2G4 is a non-peptidase member of the M24 family of metallopeptidases. This pseudoenzyme is structurally related to methionine aminopeptidases. A null mutant system based on negative selection allowed us to demonstrate that LmaPA2G4 is an essential gene in Leishmania major. Over-expression of LmaPA2G4 did not alter cell morphology or the ability to differentiate into metacyclic and amastigote stages. Interestingly, the over-expression affected cell proliferation and virulence in mouse footpad analysis. LmaPA2G4 binds a synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid [poly(I∶C)] as shown in an electrophoretic mobility shift assay (EMSA). Quantitative proteomics revealed that the over-expression of LmaPA2G4 led to accumulation of factors involved in translation initiation and elongation. Significantly, we found a strong reduction of de novo protein biosynthesis in transgenic parasites using a non-radioactive metabolic labeling assay. In conclusion, LmaPA2G4 is an essential gene and is potentially implicated in fundamental biological mechanisms, such as translation, making it an attractive target for therapeutic intervention. |
format |
Article in Journal/Newspaper |
author |
Brianna Norris-Mullins Kaitlin VanderKolk Paola Vacchina Michelle V Joyce Miguel A Morales |
author_facet |
Brianna Norris-Mullins Kaitlin VanderKolk Paola Vacchina Michelle V Joyce Miguel A Morales |
author_sort |
Brianna Norris-Mullins |
title |
LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major. |
title_short |
LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major. |
title_full |
LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major. |
title_fullStr |
LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major. |
title_full_unstemmed |
LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major. |
title_sort |
lmapa2g4, a homolog of human ebp1, is an essential gene and inhibits cell proliferation in l. major. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0002646 https://doaj.org/article/80f0aab94ffe4226a16d51308babe940 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 1, p e2646 (2014) |
op_relation |
http://europepmc.org/articles/PMC3888471?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002646 https://doaj.org/article/80f0aab94ffe4226a16d51308babe940 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002646 |
container_title |
PLoS Neglected Tropical Diseases |
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8 |
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1 |
container_start_page |
e2646 |
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1766338810609664000 |