Design of Dominant Negatives to bHLHZip Proteins that Inhibit DNA Binding
The Myc oncogene is a transcription factor that heterodimerizes with a partner protein termed Max to bind sequence-specific DNA (Blackwood and Eisenman, 1991). Both Myc and Max are members of the basic-helix-loop-helix/leucine zipper (bHLHZip) family of transcription factors (Murre, et al., 1989). The Myc/Max heterodimer binds the DNA sequence CACGTG, termed the Myc E box, and activates transcription from these sites (Blackwood, et al., 1992; Henriksson and Luscher, 1996). Provocatively, several other bHLHZip proteins, including the two USF family members and the four TFE family members, also bind and can transactivate E box DNA sequences (Desbrarats, et al., 1996). These proteins however have not been implicated in oncogenesis suggesting a more subtle mechanism exists to discriminate between the promoters relevant to cellular transformation by Myc. An unresolved question is if there is competition between different bHLHZip proteins for binding to the same cis element, with some bHLHZip proteins acting as repressors while others can act as activators, depending on the exact context of the promoter.
KeywordsBasic Region Thermal Denaturation Leucine Zipper Nuclear Localization Sequence bZIP Family
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