The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells

The MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an onco...

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Autores: Lafita Navarro, María Carmen, Liaño Pons, Judit, Quintanilla Cavia, Andrea, Varela Egocheaga, Ignacio|||0000-0002-0969-506X, Blanco Fernández, Rosa, Ourique Da Silva, Fabiana, Bretones Sánchez, Gabriel, Aresti, Julia, Molina Hoyo, Ester, Carroll, Patrick, Hurlin, Peter, Romero, Octavio A., Sánchez-Céspedes, Montse, Eisenman, Robert N., Delgado Villar, María Dolores|||0000-0003-4682-4040, León Serrano, Javier|||0000-0001-5803-0112
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/19081
Acceso en línea:http://hdl.handle.net/10902/19081
Access Level:acceso abierto
Palabra clave:MAX Dimerization Protein MLX
MAX Network Transcriptional Repressor (MNT)
MXD Family
MYC-Associated Factor X (MAX)
Myc (c-Myc)
Basic Helix-Loop-Helix Leucine Zipper Protein
Gene Regulation
Proliferation
Promoter
Transcription
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spelling The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cellsLafita Navarro, María CarmenLiaño Pons, JuditQuintanilla Cavia, AndreaVarela Egocheaga, Ignacio|||0000-0002-0969-506XBlanco Fernández, RosaOurique Da Silva, FabianaBretones Sánchez, GabrielAresti, JuliaMolina Hoyo, EsterCarroll, PatrickHurlin, PeterRomero, Octavio A.Sánchez-Céspedes, MontseEisenman, Robert N.Delgado Villar, María Dolores|||0000-0003-4682-4040León Serrano, Javier|||0000-0001-5803-0112MAX Dimerization Protein MLXMAX Network Transcriptional Repressor (MNT)MXD FamilyMYC-Associated Factor X (MAX)Myc (c-Myc)Basic Helix-Loop-Helix Leucine Zipper ProteinGene RegulationProliferationPromoterTranscriptionThe MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an oncogenic bHLH transcription factor. Upon E-box binding, the MYC-MAX dimer activates gene expression. MNT also binds to the MAX dimerization protein MLX (MLX), and MNT-MLX and MNT-MAX dimers co-exist. However, all MNT functions have been attributed to MNT-MAX dimers, and no functions of the MNT-MLX dimer have been described. MNT's biological role has been linked to its function as a MYC oncogene modulator, but little is known about its regulation. We show here that MNT localizes to the nucleus of MAX-expressing cells and that MNT-MAX dimers bind and repress the MNT promoter, an effect that depends on one of the two E-boxes on this promoter. In MAX-deficient cells, MNT was overexpressed and redistributed to the cytoplasm. Interestingly, MNT was required for cell proliferation even in the absence of MAX. We show that in MAX-deficient cells, MNT binds to MLX, but also forms homodimers. RNA-sequencing experiments revealed that MNT regulates the expression of several genes even in the absence of MAX, with many of these genes being involved in cell cycle regulation and DNA repair. Of note, MNT-MNT homodimers regulated the transcription of some genes involved in cell proliferation. The tight regulation of MNT and its functionality even without MAX suggest a major role for MNT in cell proliferation.This work was supported by Grant SAF2017-88026-R from Agencia Estatal de Investigación, Spanish Government (to J. L. and M. D. D.), funded in part by FEDER Program from the European Union, National Institutes of Health Grant CA57138/CA from NCI (to R. N. E.), and grants from Shriners Hospitals for Children (to P. J. H.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.American Society for Biochemistry and Molecular Biology Inc.Universidad de Cantabria20202020-01-09journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttp://hdl.handle.net/10902/19081Journal of Biological Chemistry, 2020, 295(7), 2001-2017reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/190812026-06-02T12:39:31Z
dc.title.none.fl_str_mv The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells
title The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells
spellingShingle The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells
Lafita Navarro, María Carmen
MAX Dimerization Protein MLX
MAX Network Transcriptional Repressor (MNT)
MXD Family
MYC-Associated Factor X (MAX)
Myc (c-Myc)
Basic Helix-Loop-Helix Leucine Zipper Protein
Gene Regulation
Proliferation
Promoter
Transcription
title_short The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells
title_full The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells
title_fullStr The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells
title_full_unstemmed The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells
title_sort The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells
dc.creator.none.fl_str_mv Lafita Navarro, María Carmen
Liaño Pons, Judit
Quintanilla Cavia, Andrea
Varela Egocheaga, Ignacio|||0000-0002-0969-506X
Blanco Fernández, Rosa
Ourique Da Silva, Fabiana
Bretones Sánchez, Gabriel
Aresti, Julia
Molina Hoyo, Ester
Carroll, Patrick
Hurlin, Peter
Romero, Octavio A.
Sánchez-Céspedes, Montse
Eisenman, Robert N.
Delgado Villar, María Dolores|||0000-0003-4682-4040
León Serrano, Javier|||0000-0001-5803-0112
author Lafita Navarro, María Carmen
author_facet Lafita Navarro, María Carmen
Liaño Pons, Judit
Quintanilla Cavia, Andrea
Varela Egocheaga, Ignacio|||0000-0002-0969-506X
Blanco Fernández, Rosa
Ourique Da Silva, Fabiana
Bretones Sánchez, Gabriel
Aresti, Julia
Molina Hoyo, Ester
Carroll, Patrick
Hurlin, Peter
Romero, Octavio A.
Sánchez-Céspedes, Montse
Eisenman, Robert N.
Delgado Villar, María Dolores|||0000-0003-4682-4040
León Serrano, Javier|||0000-0001-5803-0112
author_role author
author2 Liaño Pons, Judit
Quintanilla Cavia, Andrea
Varela Egocheaga, Ignacio|||0000-0002-0969-506X
Blanco Fernández, Rosa
Ourique Da Silva, Fabiana
Bretones Sánchez, Gabriel
Aresti, Julia
Molina Hoyo, Ester
Carroll, Patrick
Hurlin, Peter
Romero, Octavio A.
Sánchez-Céspedes, Montse
Eisenman, Robert N.
Delgado Villar, María Dolores|||0000-0003-4682-4040
León Serrano, Javier|||0000-0001-5803-0112
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv MAX Dimerization Protein MLX
MAX Network Transcriptional Repressor (MNT)
MXD Family
MYC-Associated Factor X (MAX)
Myc (c-Myc)
Basic Helix-Loop-Helix Leucine Zipper Protein
Gene Regulation
Proliferation
Promoter
Transcription
topic MAX Dimerization Protein MLX
MAX Network Transcriptional Repressor (MNT)
MXD Family
MYC-Associated Factor X (MAX)
Myc (c-Myc)
Basic Helix-Loop-Helix Leucine Zipper Protein
Gene Regulation
Proliferation
Promoter
Transcription
description The MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an oncogenic bHLH transcription factor. Upon E-box binding, the MYC-MAX dimer activates gene expression. MNT also binds to the MAX dimerization protein MLX (MLX), and MNT-MLX and MNT-MAX dimers co-exist. However, all MNT functions have been attributed to MNT-MAX dimers, and no functions of the MNT-MLX dimer have been described. MNT's biological role has been linked to its function as a MYC oncogene modulator, but little is known about its regulation. We show here that MNT localizes to the nucleus of MAX-expressing cells and that MNT-MAX dimers bind and repress the MNT promoter, an effect that depends on one of the two E-boxes on this promoter. In MAX-deficient cells, MNT was overexpressed and redistributed to the cytoplasm. Interestingly, MNT was required for cell proliferation even in the absence of MAX. We show that in MAX-deficient cells, MNT binds to MLX, but also forms homodimers. RNA-sequencing experiments revealed that MNT regulates the expression of several genes even in the absence of MAX, with many of these genes being involved in cell cycle regulation and DNA repair. Of note, MNT-MNT homodimers regulated the transcription of some genes involved in cell proliferation. The tight regulation of MNT and its functionality even without MAX suggest a major role for MNT in cell proliferation.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-09
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10902/19081
url http://hdl.handle.net/10902/19081
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology Inc.
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology Inc.
dc.source.none.fl_str_mv Journal of Biological Chemistry, 2020, 295(7), 2001-2017
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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