Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor

Isoprenyl cysteine carboxyl methyltransferase (ICMT) plays a key role in post-translational regulation of prenylated proteins. On the basis of previous results, we hypothesized that the p53 pathway and ICMT expression may be linked in cancer cells. Here, we studied whether WT p53 and cancer-associat...

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Autores: Borini Etichetti, Carla Maria, Di Benedetto, Carolina, Rossi, Carolina, Baglioni, María Virginia, Bicciato, Silvio, Del Sal, Giannino, Menacho Márquez, Mauricio Ariel, Girardini Brovelli, Javier Enrique
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/153062
Acceso en línea:http://hdl.handle.net/11336/153062
Access Level:acceso abierto
Palabra clave:PROTEIN PRENILATION
CARBOXYMETHYLATION
ICMT
MUTANT P53
CANCER
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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oai_identifier_str oai:ri.conicet.gov.ar:11336/153062
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor
title Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor
spellingShingle Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor
Borini Etichetti, Carla Maria
PROTEIN PRENILATION
CARBOXYMETHYLATION
ICMT
MUTANT P53
CANCER
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor
title_full Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor
title_fullStr Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor
title_full_unstemmed Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor
title_sort Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor
dc.creator.none.fl_str_mv Borini Etichetti, Carla Maria
Di Benedetto, Carolina
Rossi, Carolina
Baglioni, María Virginia
Bicciato, Silvio
Del Sal, Giannino
Menacho Márquez, Mauricio Ariel
Girardini Brovelli, Javier Enrique
author Borini Etichetti, Carla Maria
author_facet Borini Etichetti, Carla Maria
Di Benedetto, Carolina
Rossi, Carolina
Baglioni, María Virginia
Bicciato, Silvio
Del Sal, Giannino
Menacho Márquez, Mauricio Ariel
Girardini Brovelli, Javier Enrique
author_role author
author2 Di Benedetto, Carolina
Rossi, Carolina
Baglioni, María Virginia
Bicciato, Silvio
Del Sal, Giannino
Menacho Márquez, Mauricio Ariel
Girardini Brovelli, Javier Enrique
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PROTEIN PRENILATION
CARBOXYMETHYLATION
ICMT
MUTANT P53
CANCER
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic PROTEIN PRENILATION
CARBOXYMETHYLATION
ICMT
MUTANT P53
CANCER
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description Isoprenyl cysteine carboxyl methyltransferase (ICMT) plays a key role in post-translational regulation of prenylated proteins. On the basis of previous results, we hypothesized that the p53 pathway and ICMT expression may be linked in cancer cells. Here, we studied whether WT p53 and cancer-associated p53 point mutants regulate ICMT levels and whether ICMT overexpression affects tumor progression. Studying the effect of p53 variants on ICMT mRNA and protein levels in cancer cells, we found that WT p53 and p53 mutants differentially affect ICMT expression, indicating that p53 status influences ICMT levels in tumors. To investigate the underlying mechanisms, we constructed ICMT?luciferase reporters and found that WT p53 represses ICMT transcription. In contrast, p53 mutants showed a positive effect on ICMT expression. Promoter truncation analyses pinpointed the repressive effect of WT p53 to the 209 and 14 region on the ICMT promoter, and ChIP assays indicated that WT p53 is recruited to this region. Instead, a different promoter region was identified as responsible for the mutant p53 effect. Studying the effect of ICMT overexpression on tumor-associated phenotypes in vitro and in vivo, and analyzing breast and lung cancer databases, we identified a correlation between p53 status and ICMT expression in breast and lung cancers. Moreover, we observed that ICMT overexpression is correlated with negative clinical outcomes. Our work unveils a link between postprenylation protein processing and the p53 pathway, indicating that the functional interplay between WT and mutant p53 alters ICMT levels, thereby affecting tumor aggressiveness.
publishDate 2019
dc.date.none.fl_str_mv 2019-03
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
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/153062
Borini Etichetti, Carla Maria; Di Benedetto, Carolina; Rossi, Carolina; Baglioni, María Virginia; Bicciato, Silvio; et al.; Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry; 294; 13; 3-2019; 5060-5073
0021-9258
1083-351X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/153062
identifier_str_mv Borini Etichetti, Carla Maria; Di Benedetto, Carolina; Rossi, Carolina; Baglioni, María Virginia; Bicciato, Silvio; et al.; Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry; 294; 13; 3-2019; 5060-5073
0021-9258
1083-351X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/lookup/doi/10.1074/jbc.RA118.006037
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.RA118.006037
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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spelling Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressorBorini Etichetti, Carla MariaDi Benedetto, CarolinaRossi, CarolinaBaglioni, María VirginiaBicciato, SilvioDel Sal, GianninoMenacho Márquez, Mauricio ArielGirardini Brovelli, Javier EnriquePROTEIN PRENILATIONCARBOXYMETHYLATIONICMTMUTANT P53CANCERhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Isoprenyl cysteine carboxyl methyltransferase (ICMT) plays a key role in post-translational regulation of prenylated proteins. On the basis of previous results, we hypothesized that the p53 pathway and ICMT expression may be linked in cancer cells. Here, we studied whether WT p53 and cancer-associated p53 point mutants regulate ICMT levels and whether ICMT overexpression affects tumor progression. Studying the effect of p53 variants on ICMT mRNA and protein levels in cancer cells, we found that WT p53 and p53 mutants differentially affect ICMT expression, indicating that p53 status influences ICMT levels in tumors. To investigate the underlying mechanisms, we constructed ICMT?luciferase reporters and found that WT p53 represses ICMT transcription. In contrast, p53 mutants showed a positive effect on ICMT expression. Promoter truncation analyses pinpointed the repressive effect of WT p53 to the 209 and 14 region on the ICMT promoter, and ChIP assays indicated that WT p53 is recruited to this region. Instead, a different promoter region was identified as responsible for the mutant p53 effect. Studying the effect of ICMT overexpression on tumor-associated phenotypes in vitro and in vivo, and analyzing breast and lung cancer databases, we identified a correlation between p53 status and ICMT expression in breast and lung cancers. Moreover, we observed that ICMT overexpression is correlated with negative clinical outcomes. Our work unveils a link between postprenylation protein processing and the p53 pathway, indicating that the functional interplay between WT and mutant p53 alters ICMT levels, thereby affecting tumor aggressiveness.Fil: Borini Etichetti, Carla Maria. 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: Di Benedetto, Carolina. 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: Rossi, Carolina. 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: Baglioni, María Virginia. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Bicciato, Silvio. Università di Modena e Reggio Emilia; ItaliaFil: Del Sal, Giannino. Laboratorio Nazionale del Consorzio Interuniversitario delle Biotecnologie Area di Ricerca; Italia. Università degli Studi di Trieste; ItaliaFil: Menacho Márquez, Mauricio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; ArgentinaFil: Girardini Brovelli, Javier Enrique. 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; ArgentinaAmerican Society for Biochemistry and Molecular Biology2019-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/153062Borini Etichetti, Carla Maria; Di Benedetto, Carolina; Rossi, Carolina; Baglioni, María Virginia; Bicciato, Silvio; et al.; Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry; 294; 13; 3-2019; 5060-50730021-92581083-351XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/lookup/doi/10.1074/jbc.RA118.006037info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.RA118.006037info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:40:33Zoai:ri.conicet.gov.ar:11336/153062instacron: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:34982024-05-08 13:40:33.308CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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