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bHLH-Orange Transcription Factors in Development and Cancer

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Author(s): Hong Sun | Saghi Ghaffari | Reshma Taneja

Journal: Translational Oncogenomics
ISSN 1177-2727

Volume: 2;
Start page: 105;
Date: 2007;
Original page

Keywords: bHLH-Orange | differentiation | knockout | p53 | Hypoxia inducible factor-1 | cancer

ABSTRACT
Basic helix-loop-helix (bHLH) proteins are a large superfamily of transcription factors that play critical roles in many physiological processes including cellular differentiation, cell cycle arrest and apoptosis. Based on structural and phylogenetic analysis, mammalian bHLH-Orange (bHLH-O) proteins, which constitute the repressor family of bHLH factors, can be grouped into four subfamilies: Hes, Hey, Helt and Stra13/Dec. In addition to the bHLH domain that mediates DNA-binding and protein dimerization, all members of this family are characterized by a distinctive motif called the “Orange domain” which is present exclusively in these factors. Genetic studies using targeted mutagenesis in mice have revealed essential roles for many bHLH-O genes in embryonic development, cell fate decisions, differentiation of a number of cell types and in apoptosis. Furthermore, growing evidence of crosstalk between bHLH-O proteins with the tumor suppressors p53 and hypoxia-inducible factor, have started to shed light on their possible roles in oncogenesis. Consistently, deregulated expression of several bHLH-O factors is associated with various human cancers. Here, we review the structure and biological functions of bHLH-O factors, and discuss recent studies that suggest a potential role for these factors in tumorigenesis and tumor progression.
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