Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana
- Autores
- Vazquez, Maria Magdalena; Goldy, Camila; Rodriguez, Ramiro; Casalongue, Claudia; Paris, Ramiro
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- The mevalonate pathway catalyzes the de novo synthesis of cholesterol, but also provides isoprenoids that may be used for protein modification through a complex process known as prenylation. Some proteins involved in oncogenic processes, such as Ras and Rho GTPases are among the targets of this modification. Pioneering studies with statins have suggested that mevalonate pathway alteration cooperates with tumor aggressiveness. More recently, other evidence has confirmed that alteration of this pathway may promote aggressive phenotypes and pointed out at enhanced protein prenylation as a possible mechanism underlying this effect. ICMT plays a central role in this posttranslational modification process by catalyzing the last step, carboxymethylation of the prenylated C-terminus in target proteins. We have recently unveiled a link between post-prenylation processing and the p53 pathway by showing that ICMT expression is repressed by wt p53, but enhanced by cancer-associated p53 point mutants. Moreover, our analysis of Breast and Lung cancer databases showed a negative correlation between ICMT expression and wt p53 status. Moreover, we found a significantly decreased metastasis-free survival frequency in patients with high ICMT expression. Basing on these results, we wondered if alteration of ICMT levels enhances metastasis development. To answer this question, we studied the effect of ICMT overexpression on metastasis in vivo, using Triple Negative Breast Cancer cells in an immunocompetent mouse model. We extended our previous analysis on breast cancer patients and we found that p53 status affects the impact of ICMT overexpression on clinical outcomes. Besides, our studies on the regulation of ICMT expression showed that other p53 family members affect its transcription. Our results suggest that ICMT levels are affected by alterations in the functional equilibrium between different members of this family during tumor progression. To explore the potential of pharmacological manipulation of ICMT function, we analyzed the impact of the ICMT inhibitor Cysmethynil to affect tumor-associated phenotypes. We found that ICMT inhibition affects clonogenic potential, as well as phenotypes associated with metastatic cells, such as migration and invasion in vitro. In an effort to develop novel ICMT inhibitors and inspired on Salirasib (S-trans-trans-farnesylthiosalicylic acid) we synthesized novel thiosalicylic acid derivatives. As a preliminary characterization, we analyzed the antiproliferative activity of our compounds in vitro on MDA-MB-231 cells. Our results suggest that ICMT overexpression affects tumor progression and that molecules interfering with the function of prenylated proteins are potentially useful in therapeutic strategies.
Fil: Vazquez, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
Fil: Goldy, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Rodriguez, Ramiro. Universidad Nacional de Rosario. Centro de Estudios Interdisciplinarios; Argentina
Fil: Casalongue, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
Fil: Paris, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
The LV Annual SAIB Meeting and XIV PABMB Congress
Salta
Argentina
Sociedad Argentina de Investigación Bioquímica y Biología Molecular - Materia
-
ARABIDOPSIS THALIANA
AUXIN
GRAVITROPISM
NITRIC OXIDE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/154047
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Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thalianaVazquez, Maria MagdalenaGoldy, CamilaRodriguez, RamiroCasalongue, ClaudiaParis, RamiroARABIDOPSIS THALIANAAUXINGRAVITROPISMNITRIC OXIDEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The mevalonate pathway catalyzes the de novo synthesis of cholesterol, but also provides isoprenoids that may be used for protein modification through a complex process known as prenylation. Some proteins involved in oncogenic processes, such as Ras and Rho GTPases are among the targets of this modification. Pioneering studies with statins have suggested that mevalonate pathway alteration cooperates with tumor aggressiveness. More recently, other evidence has confirmed that alteration of this pathway may promote aggressive phenotypes and pointed out at enhanced protein prenylation as a possible mechanism underlying this effect. ICMT plays a central role in this posttranslational modification process by catalyzing the last step, carboxymethylation of the prenylated C-terminus in target proteins. We have recently unveiled a link between post-prenylation processing and the p53 pathway by showing that ICMT expression is repressed by wt p53, but enhanced by cancer-associated p53 point mutants. Moreover, our analysis of Breast and Lung cancer databases showed a negative correlation between ICMT expression and wt p53 status. Moreover, we found a significantly decreased metastasis-free survival frequency in patients with high ICMT expression. Basing on these results, we wondered if alteration of ICMT levels enhances metastasis development. To answer this question, we studied the effect of ICMT overexpression on metastasis in vivo, using Triple Negative Breast Cancer cells in an immunocompetent mouse model. We extended our previous analysis on breast cancer patients and we found that p53 status affects the impact of ICMT overexpression on clinical outcomes. Besides, our studies on the regulation of ICMT expression showed that other p53 family members affect its transcription. Our results suggest that ICMT levels are affected by alterations in the functional equilibrium between different members of this family during tumor progression. To explore the potential of pharmacological manipulation of ICMT function, we analyzed the impact of the ICMT inhibitor Cysmethynil to affect tumor-associated phenotypes. We found that ICMT inhibition affects clonogenic potential, as well as phenotypes associated with metastatic cells, such as migration and invasion in vitro. In an effort to develop novel ICMT inhibitors and inspired on Salirasib (S-trans-trans-farnesylthiosalicylic acid) we synthesized novel thiosalicylic acid derivatives. As a preliminary characterization, we analyzed the antiproliferative activity of our compounds in vitro on MDA-MB-231 cells. Our results suggest that ICMT overexpression affects tumor progression and that molecules interfering with the function of prenylated proteins are potentially useful in therapeutic strategies.Fil: Vazquez, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Goldy, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Rodriguez, Ramiro. Universidad Nacional de Rosario. Centro de Estudios Interdisciplinarios; ArgentinaFil: Casalongue, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Paris, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaThe LV Annual SAIB Meeting and XIV PABMB CongressSaltaArgentinaSociedad Argentina de Investigación Bioquímica y Biología MolecularTech Science Press2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/154047Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana; The LV Annual SAIB Meeting and XIV PABMB Congress; Salta; Argentina; 2019; 61-611667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.saib.org.ar/index.php?q=node/562Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:37Zoai:ri.conicet.gov.ar:11336/154047instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:47:37.991CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana |
title |
Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana |
spellingShingle |
Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana Vazquez, Maria Magdalena ARABIDOPSIS THALIANA AUXIN GRAVITROPISM NITRIC OXIDE |
title_short |
Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana |
title_full |
Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana |
title_fullStr |
Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana |
title_full_unstemmed |
Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana |
title_sort |
Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana |
dc.creator.none.fl_str_mv |
Vazquez, Maria Magdalena Goldy, Camila Rodriguez, Ramiro Casalongue, Claudia Paris, Ramiro |
author |
Vazquez, Maria Magdalena |
author_facet |
Vazquez, Maria Magdalena Goldy, Camila Rodriguez, Ramiro Casalongue, Claudia Paris, Ramiro |
author_role |
author |
author2 |
Goldy, Camila Rodriguez, Ramiro Casalongue, Claudia Paris, Ramiro |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
ARABIDOPSIS THALIANA AUXIN GRAVITROPISM NITRIC OXIDE |
topic |
ARABIDOPSIS THALIANA AUXIN GRAVITROPISM NITRIC OXIDE |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
The mevalonate pathway catalyzes the de novo synthesis of cholesterol, but also provides isoprenoids that may be used for protein modification through a complex process known as prenylation. Some proteins involved in oncogenic processes, such as Ras and Rho GTPases are among the targets of this modification. Pioneering studies with statins have suggested that mevalonate pathway alteration cooperates with tumor aggressiveness. More recently, other evidence has confirmed that alteration of this pathway may promote aggressive phenotypes and pointed out at enhanced protein prenylation as a possible mechanism underlying this effect. ICMT plays a central role in this posttranslational modification process by catalyzing the last step, carboxymethylation of the prenylated C-terminus in target proteins. We have recently unveiled a link between post-prenylation processing and the p53 pathway by showing that ICMT expression is repressed by wt p53, but enhanced by cancer-associated p53 point mutants. Moreover, our analysis of Breast and Lung cancer databases showed a negative correlation between ICMT expression and wt p53 status. Moreover, we found a significantly decreased metastasis-free survival frequency in patients with high ICMT expression. Basing on these results, we wondered if alteration of ICMT levels enhances metastasis development. To answer this question, we studied the effect of ICMT overexpression on metastasis in vivo, using Triple Negative Breast Cancer cells in an immunocompetent mouse model. We extended our previous analysis on breast cancer patients and we found that p53 status affects the impact of ICMT overexpression on clinical outcomes. Besides, our studies on the regulation of ICMT expression showed that other p53 family members affect its transcription. Our results suggest that ICMT levels are affected by alterations in the functional equilibrium between different members of this family during tumor progression. To explore the potential of pharmacological manipulation of ICMT function, we analyzed the impact of the ICMT inhibitor Cysmethynil to affect tumor-associated phenotypes. We found that ICMT inhibition affects clonogenic potential, as well as phenotypes associated with metastatic cells, such as migration and invasion in vitro. In an effort to develop novel ICMT inhibitors and inspired on Salirasib (S-trans-trans-farnesylthiosalicylic acid) we synthesized novel thiosalicylic acid derivatives. As a preliminary characterization, we analyzed the antiproliferative activity of our compounds in vitro on MDA-MB-231 cells. Our results suggest that ICMT overexpression affects tumor progression and that molecules interfering with the function of prenylated proteins are potentially useful in therapeutic strategies. Fil: Vazquez, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina Fil: Goldy, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Rodriguez, Ramiro. Universidad Nacional de Rosario. Centro de Estudios Interdisciplinarios; Argentina Fil: Casalongue, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina Fil: Paris, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina The LV Annual SAIB Meeting and XIV PABMB Congress Salta Argentina Sociedad Argentina de Investigación Bioquímica y Biología Molecular |
description |
The mevalonate pathway catalyzes the de novo synthesis of cholesterol, but also provides isoprenoids that may be used for protein modification through a complex process known as prenylation. Some proteins involved in oncogenic processes, such as Ras and Rho GTPases are among the targets of this modification. Pioneering studies with statins have suggested that mevalonate pathway alteration cooperates with tumor aggressiveness. More recently, other evidence has confirmed that alteration of this pathway may promote aggressive phenotypes and pointed out at enhanced protein prenylation as a possible mechanism underlying this effect. ICMT plays a central role in this posttranslational modification process by catalyzing the last step, carboxymethylation of the prenylated C-terminus in target proteins. We have recently unveiled a link between post-prenylation processing and the p53 pathway by showing that ICMT expression is repressed by wt p53, but enhanced by cancer-associated p53 point mutants. Moreover, our analysis of Breast and Lung cancer databases showed a negative correlation between ICMT expression and wt p53 status. Moreover, we found a significantly decreased metastasis-free survival frequency in patients with high ICMT expression. Basing on these results, we wondered if alteration of ICMT levels enhances metastasis development. To answer this question, we studied the effect of ICMT overexpression on metastasis in vivo, using Triple Negative Breast Cancer cells in an immunocompetent mouse model. We extended our previous analysis on breast cancer patients and we found that p53 status affects the impact of ICMT overexpression on clinical outcomes. Besides, our studies on the regulation of ICMT expression showed that other p53 family members affect its transcription. Our results suggest that ICMT levels are affected by alterations in the functional equilibrium between different members of this family during tumor progression. To explore the potential of pharmacological manipulation of ICMT function, we analyzed the impact of the ICMT inhibitor Cysmethynil to affect tumor-associated phenotypes. We found that ICMT inhibition affects clonogenic potential, as well as phenotypes associated with metastatic cells, such as migration and invasion in vitro. In an effort to develop novel ICMT inhibitors and inspired on Salirasib (S-trans-trans-farnesylthiosalicylic acid) we synthesized novel thiosalicylic acid derivatives. As a preliminary characterization, we analyzed the antiproliferative activity of our compounds in vitro on MDA-MB-231 cells. Our results suggest that ICMT overexpression affects tumor progression and that molecules interfering with the function of prenylated proteins are potentially useful in therapeutic strategies. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/conferenceObject Reunión Journal http://purl.org/coar/resource_type/c_5794 info:ar-repo/semantics/documentoDeConferencia |
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publishedVersion |
format |
conferenceObject |
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http://hdl.handle.net/11336/154047 Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana; The LV Annual SAIB Meeting and XIV PABMB Congress; Salta; Argentina; 2019; 61-61 1667-5746 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/154047 |
identifier_str_mv |
Nitric oxide and auxin regulate root meristem during gravitropism in Arabidopsis thaliana; The LV Annual SAIB Meeting and XIV PABMB Congress; Salta; Argentina; 2019; 61-61 1667-5746 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
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info:eu-repo/semantics/altIdentifier/url/http://www.saib.org.ar/index.php?q=node/562 |
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Internacional |
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Tech Science Press |
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Tech Science Press |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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