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dc.contributor.author
Racca, Ana Cristina  
dc.contributor.author
Prucca, Cesar German  
dc.contributor.author
Caputto, Beatriz Leonor  
dc.date.available
2021-03-24T15:02:54Z  
dc.date.issued
2019-06  
dc.identifier.citation
Racca, Ana Cristina; Prucca, Cesar German; Caputto, Beatriz Leonor; Fra-1 and c-Fos N-terminal deletion mutants impair breast tumor cell proliferation by blocking lipid synthesis activation; Frontiers Media S.A.; Frontiers in Oncology; 9; JUN; 6-2019; 1-12  
dc.identifier.uri
http://hdl.handle.net/11336/128859  
dc.description.abstract
Tumor cells require high rates of lipid synthesis to support membrane biogenesis for their exacerbated growth. The only two proteins known that activate phospholipid synthesis are Fra-1 and c-Fos, two members of the AP-1 family of transcription factors. These proteins that are overexpressed in human breast malignant tumors increase the rate of phospholipid synthesis at the endoplasmic reticulum through a mechanism independent of their nuclear function. The aim of this study was to inhibit breast tumor cell proliferation by modulating c-Fos and Fra-1 and regulate membrane biogenesis by controlling lipid synthesis rates. The molecular mechanism by which Fra-1 and c-Fos activate phospholipid synthesis was examined. Both proteins physically associate with the rate limiting enzyme CDP-DAG synthase through their N-terminus domain and activate it through their basic domain; neither protein associates to or activates the enzyme phosphatidylinositol synthase as determined through in vitro enzymatic reactions and FRET experiments. The N-terminus domain of both proteins act as negative dominant peptides that physically associate with CDP-DAG synthase but do not activate it. Proliferation of MDA-MB231 and 4T1 cells was impaired in vitro after inducing them to proliferate in the presence of the negative dominant peptides derived from Fra-1 and c-Fos. When tumors generated in Balb/c mice with the breast tumor cell line 4T1 were treated with these negative dominant peptides, a significant reduction in tumor growth was observed. Consequently, these Fra-1 and c-Fos negative dominant peptides can be exploited as a new therapeutic strategy to impair breast tumor cell proliferation.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Frontiers Media S.A.  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
C-FOS  
dc.subject
CDP-DIACYLGLYCEROL SYNTHASE  
dc.subject
FRA-1  
dc.subject
PHOSPHATIDYLINOSITOL SYNTHASE  
dc.subject
PHOSPHOLIPIDS  
dc.subject.classification
Bioquímica y Biología Molecular  
dc.subject.classification
Ciencias Biológicas  
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS  
dc.title
Fra-1 and c-Fos N-terminal deletion mutants impair breast tumor cell proliferation by blocking lipid synthesis activation  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2020-11-20T19:59:05Z  
dc.identifier.eissn
2234-943X  
dc.journal.volume
9  
dc.journal.number
JUN  
dc.journal.pagination
1-12  
dc.journal.pais
Suiza  
dc.journal.ciudad
Lausana  
dc.description.fil
Fil: Racca, Ana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina  
dc.description.fil
Fil: Prucca, Cesar German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina  
dc.description.fil
Fil: Caputto, Beatriz Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina  
dc.journal.title
Frontiers in Oncology  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fonc.2019.00544/full  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.3389/fonc.2019.00544