Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor.

Détails

ID Serval
serval:BIB_EC979EBC91F2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor.
Périodique
EMBO Journal
Auteur(s)
Meroni G., Reymond A., Alcalay M., Borsani G., Tanigami A., Tonlorenzi R., Lo Nigro C., Messali S., Zollo M., Ledbetter D.H., Brent R., Ballabio A., Carrozzo R.
ISSN
0261-4189 (Print)
ISSN-L
0261-4189
Statut éditorial
Publié
Date de publication
1997
Volume
16
Numéro
10
Pages
2892-2906
Langue
anglais
Résumé
Proteins of the Myc and Mad family are involved in transcriptional regulation and mediate cell differentiation and proliferation. These molecules share a basic-helix-loop-helix leucine zipper domain (bHLHZip) and bind DNA at the E box (CANNTG) consensus by forming heterodimers with Max. We report the isolation, characterization and mapping of a human gene and its mouse homolog encoding a new member of this family of proteins, named Rox. Through interaction mating and immunoprecipitation techniques, we demonstrate that Rox heterodimerizes with Max and weakly homodimerizes. Interestingly, bandshift assays demonstrate that the Rox-Max heterodimer shows a novel DNA binding specificity, having a higher affinity for the CACGCG site compared with the canonical E box CACGTG site. Transcriptional studies indicate that Rox represses transcription in both human HEK293 cells and yeast. We demonstrate that repression in yeast is through interaction between the N-terminus of the protein and the Sin3 co-repressor, as previously shown for the other Mad family members. ROX is highly expressed in quiescent fibroblasts and expression markedly decreases when cells enter the cell cycle. Moreover, ROX expression appears to be induced in U937 myeloid leukemia cells stimulated to differentiate with 12-O-tetradecanoylphorbol-13-acetate. The identification of a novel Max-interacting protein adds an important piece to the puzzle of Myc/Max/Mad coordinated action and function in normal and pathological situations. Furthermore, mapping of the human gene to chromosome 17p13.3 in a region that frequently undergoes loss of heterozygosity in a number of malignancies, together with the biochemical and expression features, suggest involvement of ROX in human neoplasia.
Mots-clé
Amino Acid Sequence, Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Basic-Leucine Zipper Transcription Factors, Binding Sites, Chromosome Mapping, Chromosomes, Human, Pair 17, Cloning, Molecular, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Dimerization, Gene Expression Regulation, Helix-Loop-Helix Motifs/genetics, Histone Deacetylases, Humans, Leucine Zippers/genetics, Mice, Molecular Sequence Data, Nuclear Proteins/genetics, Protein Binding, Proto-Oncogene Proteins c-myc/genetics, Repressor Proteins/genetics, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Transcription Factors/metabolism, Transcription, Genetic
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 16:52
Dernière modification de la notice
20/08/2019 17:14
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