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

Abstract: 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.

 Fuente: J Biol Chem . 2020 Feb 14;295(7):2001-2017. doi: 10.1074/jbc.RA119.010389.

Editorial: American Society for Biochemistry and Molecular Biology Inc.

 Fecha de publicación: 09/01/2020

Nº de páginas: 107

Tipo de publicación: Artículo de Revista

 DOI: 10.1074/jbc.RA119.010389

ISSN: 0021-9258,1083-351X

Proyecto español: SAF2017-88026-R

Url de la publicación: https://doi.org/10.1074/jbc.ra119.010389

Autores/as

MARIA DEL CARMEN LAFITA NAVARRO

JUDIT LIAÑO PONS

ANDREA QUINTANILLA CAVIA

FABIANA OURIQUE DA SILVA

GABRIEL BRETONES SANCHEZ

ARESTI, JULIA

ESTER MOLINA HOYO

CARROLL, PATRICK

HURLIN, PETER

ROMERO, OCTAVIO A.

SÁNCHEZ-CÉSPEDES, MONTSE

EISENMAN, ROBERT N.