The subcellular localization of the ChoRE-binding protein, encoded by the Williams-Beuren syndrome critical region gene 14, is regulated by 14-3-3

Giuseppe Merla, Cédric Howald, Stylianos E. Antonarakis, Alexandre Reymond

Research output: Contribution to journalArticle

Abstract

The Williams-Beuren syndrome (WBS) is a contiguous gene syndrome caused by chromosomal rearrangements at chromosome band 7q11.23. Several endocrine phenotypes, in particular impaired glucose tolerance and silent diabetes, have been described for this clinically complex disorder. The WBSCR14gene, one of the genes mapping to the WBS critical region, encodes a member of the basic-helix-loop-helix leucine zipper family of transcription factors, which dimerizes with the Max-like protein, Mix. This heterodimeric complex binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoter of lipogenic enzymes. We identified five novel WBSCR14-interacting proteins, four 14-3-3 isotypes and NIF3L1, which form a single polypeptide complex in mammalian cells. Phosphatase treatment abrogates the association between WBSCR14 and 14-3-3, as shown previously for multiple 14-3-3 interactors. WBSCR14 is exported actively from the nucleus through a CRM1-dependent mechanism. This translocation is contingent upon the ability to bind 14-3-3. Through this mechanism the 14-3-3 isotypes directly affect the WBSCR14:Mlx complexes, which activate the transcription of lipogenic genes.

Original languageEnglish
Pages (from-to)1505-1514
Number of pages10
JournalHuman Molecular Genetics
Volume13
Issue number14
DOIs
Publication statusPublished - Jul 15 2004

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Williams Syndrome
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Carrier Proteins
14-3-3 Proteins
Glucose Intolerance
Chromosome Mapping
Response Elements
Phosphoric Monoester Hydrolases
Genes
Chromosomes
Carbohydrates
Phenotype
Glucose
Peptides
Enzymes
Therapeutics
Myc associated factor X

ASJC Scopus subject areas

  • Genetics

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The subcellular localization of the ChoRE-binding protein, encoded by the Williams-Beuren syndrome critical region gene 14, is regulated by 14-3-3. / Merla, Giuseppe; Howald, Cédric; Antonarakis, Stylianos E.; Reymond, Alexandre.

In: Human Molecular Genetics, Vol. 13, No. 14, 15.07.2004, p. 1505-1514.

Research output: Contribution to journalArticle

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