Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1
- Autores
- Lopez, Maria Belen; Garcia, Maria Noé; Grasso, Daniel Hector; Bintz, Jennifer; Molejon, Maria Ines; Velez, Gabriel; Lomberk, Gwen; Neira, Jose Luis; Urrutia, Raul; Iovanna, Juan Lucio
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- We have previously demonstrated a crucial role of nuclear protein 1 (NUPR1) in tumor development and progression. In this work, we report the functional characterization of a novel Nupr1-like isoform (NUPR1L) and its functional interaction with the protumoral factor NUPR1. Through the use of primary sequence analysis, threading, and homology-based molecular modeling, as well as expression and immunolocalization, studies reveal that NUPR1L displays properties, which are similar to member of the HMG-like family of chromatin regulators, including its ability to translocate to the cell nucleus and bind to DNA. Analysis of the NUPR1L promoter showed the presence of two p53-response elements at positions -37 and -7, respectively. Experiments using reporter assays combined with site-directed mutagenesis and using cells with controllable p53 expression demonstrate that both of these sequences are responsible for the regulation of NUPR1L expression by p53. Congruently, NUPR1L gene expression is activated in response to DNA damage induced by oxaliplatin treatment or cell cycle arrest induced by serum starvation, two well-validated methods to achieve p53 activation. Interestingly, expression of NUPR1L downregulates the expression of NUPR1, its closely related protumoral isoform, by a mechanism that involves the inhibition of its promoter activity. At the cellular level, overexpression of NUPR1L induces G1 cell cycle arrest and a decrease in their cell viability, an effect that is mediated, at least in part, by downregulating NUPR1 expression. Combined, these experiments constitute the first functional characterization of NUPR1L as a new p53-induced gene, which negatively regulates the protumoral factor NUPR1.
Fil: Lopez, Maria Belen. Centre de Recherche En Cancerologie de Marseille; Francia
Fil: Garcia, Maria Noé. Centre de Recherche En Cancerologie de Marseille; Francia
Fil: Grasso, Daniel Hector. Centre de Recherche En Cancerologie de Marseille; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bintz, Jennifer. Centre de Recherche En Cancerologie de Marseille; Francia
Fil: Molejon, Maria Ines. Centre de Recherche En Cancerologie de Marseille; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Velez, Gabriel. Mayo Clinic; Estados Unidos
Fil: Lomberk, Gwen. Mayo Clinic; Estados Unidos
Fil: Neira, Jose Luis. Universidad de Miguel Hernández; España
Fil: Urrutia, Raul. Mayo Clinic; Estados Unidos
Fil: Iovanna, Juan. Centre de Recherche En Cancerologie de Marseille; Francia - Materia
-
P53-Dependent Gene
Stress Gene
Dna Damage
Nupr1l
Nupr1
P53 - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/38797
Ver los metadatos del registro completo
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Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1Lopez, Maria BelenGarcia, Maria NoéGrasso, Daniel HectorBintz, JenniferMolejon, Maria InesVelez, GabrielLomberk, GwenNeira, Jose LuisUrrutia, RaulIovanna, Juan LucioP53-Dependent GeneStress GeneDna DamageNupr1lNupr1P53https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We have previously demonstrated a crucial role of nuclear protein 1 (NUPR1) in tumor development and progression. In this work, we report the functional characterization of a novel Nupr1-like isoform (NUPR1L) and its functional interaction with the protumoral factor NUPR1. Through the use of primary sequence analysis, threading, and homology-based molecular modeling, as well as expression and immunolocalization, studies reveal that NUPR1L displays properties, which are similar to member of the HMG-like family of chromatin regulators, including its ability to translocate to the cell nucleus and bind to DNA. Analysis of the NUPR1L promoter showed the presence of two p53-response elements at positions -37 and -7, respectively. Experiments using reporter assays combined with site-directed mutagenesis and using cells with controllable p53 expression demonstrate that both of these sequences are responsible for the regulation of NUPR1L expression by p53. Congruently, NUPR1L gene expression is activated in response to DNA damage induced by oxaliplatin treatment or cell cycle arrest induced by serum starvation, two well-validated methods to achieve p53 activation. Interestingly, expression of NUPR1L downregulates the expression of NUPR1, its closely related protumoral isoform, by a mechanism that involves the inhibition of its promoter activity. At the cellular level, overexpression of NUPR1L induces G1 cell cycle arrest and a decrease in their cell viability, an effect that is mediated, at least in part, by downregulating NUPR1 expression. Combined, these experiments constitute the first functional characterization of NUPR1L as a new p53-induced gene, which negatively regulates the protumoral factor NUPR1.Fil: Lopez, Maria Belen. Centre de Recherche En Cancerologie de Marseille; FranciaFil: Garcia, Maria Noé. Centre de Recherche En Cancerologie de Marseille; FranciaFil: Grasso, Daniel Hector. Centre de Recherche En Cancerologie de Marseille; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bintz, Jennifer. Centre de Recherche En Cancerologie de Marseille; FranciaFil: Molejon, Maria Ines. Centre de Recherche En Cancerologie de Marseille; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Velez, Gabriel. Mayo Clinic; Estados UnidosFil: Lomberk, Gwen. Mayo Clinic; Estados UnidosFil: Neira, Jose Luis. Universidad de Miguel Hernández; EspañaFil: Urrutia, Raul. Mayo Clinic; Estados UnidosFil: Iovanna, Juan. Centre de Recherche En Cancerologie de Marseille; FranciaWiley-liss, Div John Wiley & Sons Inc2015-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38797Lopez, Maria Belen; Garcia, Maria Noé; Grasso, Daniel Hector; Bintz, Jennifer; Molejon, Maria Ines; et al.; Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1; Wiley-liss, Div John Wiley & Sons Inc; Journal of Cellular Physiology; 230; 12; 12-2015; 2936-29500021-9541CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.25022info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.25022info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:23:05Zoai:ri.conicet.gov.ar:11336/38797instacron: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:34982025-10-15 15:23:05.63CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1 |
| title |
Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1 |
| spellingShingle |
Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1 Lopez, Maria Belen P53-Dependent Gene Stress Gene Dna Damage Nupr1l Nupr1 P53 |
| title_short |
Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1 |
| title_full |
Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1 |
| title_fullStr |
Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1 |
| title_full_unstemmed |
Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1 |
| title_sort |
Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1 |
| dc.creator.none.fl_str_mv |
Lopez, Maria Belen Garcia, Maria Noé Grasso, Daniel Hector Bintz, Jennifer Molejon, Maria Ines Velez, Gabriel Lomberk, Gwen Neira, Jose Luis Urrutia, Raul Iovanna, Juan Lucio |
| author |
Lopez, Maria Belen |
| author_facet |
Lopez, Maria Belen Garcia, Maria Noé Grasso, Daniel Hector Bintz, Jennifer Molejon, Maria Ines Velez, Gabriel Lomberk, Gwen Neira, Jose Luis Urrutia, Raul Iovanna, Juan Lucio |
| author_role |
author |
| author2 |
Garcia, Maria Noé Grasso, Daniel Hector Bintz, Jennifer Molejon, Maria Ines Velez, Gabriel Lomberk, Gwen Neira, Jose Luis Urrutia, Raul Iovanna, Juan Lucio |
| author2_role |
author author author author author author author author author |
| dc.subject.none.fl_str_mv |
P53-Dependent Gene Stress Gene Dna Damage Nupr1l Nupr1 P53 |
| topic |
P53-Dependent Gene Stress Gene Dna Damage Nupr1l Nupr1 P53 |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
We have previously demonstrated a crucial role of nuclear protein 1 (NUPR1) in tumor development and progression. In this work, we report the functional characterization of a novel Nupr1-like isoform (NUPR1L) and its functional interaction with the protumoral factor NUPR1. Through the use of primary sequence analysis, threading, and homology-based molecular modeling, as well as expression and immunolocalization, studies reveal that NUPR1L displays properties, which are similar to member of the HMG-like family of chromatin regulators, including its ability to translocate to the cell nucleus and bind to DNA. Analysis of the NUPR1L promoter showed the presence of two p53-response elements at positions -37 and -7, respectively. Experiments using reporter assays combined with site-directed mutagenesis and using cells with controllable p53 expression demonstrate that both of these sequences are responsible for the regulation of NUPR1L expression by p53. Congruently, NUPR1L gene expression is activated in response to DNA damage induced by oxaliplatin treatment or cell cycle arrest induced by serum starvation, two well-validated methods to achieve p53 activation. Interestingly, expression of NUPR1L downregulates the expression of NUPR1, its closely related protumoral isoform, by a mechanism that involves the inhibition of its promoter activity. At the cellular level, overexpression of NUPR1L induces G1 cell cycle arrest and a decrease in their cell viability, an effect that is mediated, at least in part, by downregulating NUPR1 expression. Combined, these experiments constitute the first functional characterization of NUPR1L as a new p53-induced gene, which negatively regulates the protumoral factor NUPR1. Fil: Lopez, Maria Belen. Centre de Recherche En Cancerologie de Marseille; Francia Fil: Garcia, Maria Noé. Centre de Recherche En Cancerologie de Marseille; Francia Fil: Grasso, Daniel Hector. Centre de Recherche En Cancerologie de Marseille; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bintz, Jennifer. Centre de Recherche En Cancerologie de Marseille; Francia Fil: Molejon, Maria Ines. Centre de Recherche En Cancerologie de Marseille; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Velez, Gabriel. Mayo Clinic; Estados Unidos Fil: Lomberk, Gwen. Mayo Clinic; Estados Unidos Fil: Neira, Jose Luis. Universidad de Miguel Hernández; España Fil: Urrutia, Raul. Mayo Clinic; Estados Unidos Fil: Iovanna, Juan. Centre de Recherche En Cancerologie de Marseille; Francia |
| description |
We have previously demonstrated a crucial role of nuclear protein 1 (NUPR1) in tumor development and progression. In this work, we report the functional characterization of a novel Nupr1-like isoform (NUPR1L) and its functional interaction with the protumoral factor NUPR1. Through the use of primary sequence analysis, threading, and homology-based molecular modeling, as well as expression and immunolocalization, studies reveal that NUPR1L displays properties, which are similar to member of the HMG-like family of chromatin regulators, including its ability to translocate to the cell nucleus and bind to DNA. Analysis of the NUPR1L promoter showed the presence of two p53-response elements at positions -37 and -7, respectively. Experiments using reporter assays combined with site-directed mutagenesis and using cells with controllable p53 expression demonstrate that both of these sequences are responsible for the regulation of NUPR1L expression by p53. Congruently, NUPR1L gene expression is activated in response to DNA damage induced by oxaliplatin treatment or cell cycle arrest induced by serum starvation, two well-validated methods to achieve p53 activation. Interestingly, expression of NUPR1L downregulates the expression of NUPR1, its closely related protumoral isoform, by a mechanism that involves the inhibition of its promoter activity. At the cellular level, overexpression of NUPR1L induces G1 cell cycle arrest and a decrease in their cell viability, an effect that is mediated, at least in part, by downregulating NUPR1 expression. Combined, these experiments constitute the first functional characterization of NUPR1L as a new p53-induced gene, which negatively regulates the protumoral factor NUPR1. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015-12 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/38797 Lopez, Maria Belen; Garcia, Maria Noé; Grasso, Daniel Hector; Bintz, Jennifer; Molejon, Maria Ines; et al.; Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1; Wiley-liss, Div John Wiley & Sons Inc; Journal of Cellular Physiology; 230; 12; 12-2015; 2936-2950 0021-9541 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/38797 |
| identifier_str_mv |
Lopez, Maria Belen; Garcia, Maria Noé; Grasso, Daniel Hector; Bintz, Jennifer; Molejon, Maria Ines; et al.; Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1; Wiley-liss, Div John Wiley & Sons Inc; Journal of Cellular Physiology; 230; 12; 12-2015; 2936-2950 0021-9541 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.25022 info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.25022 |
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Wiley-liss, Div John Wiley & Sons Inc |
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Wiley-liss, Div John Wiley & Sons Inc |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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