title: Lack of transcriptional repression by max homodimers.
abstract: Max, a basic-helix-loop-helix-leucine zipper (bHLH-ZIP) protein, plays a central role in the transcriptional regulation of myc oncoprotein-responsive genes. Myc-max heterodimers bind to consensus E-box motifs near or within the promoters of these genes and activate gene expression, whereas heterodimers between max and members of the mad family of bHLH-ZIP proteins promote transcriptional repression. In contrast to all other members of the myc network, max readily homodimerizes and binds to identical E-box sites in vitro. However, the role for max homodimers in transcriptional repression in vivo is unclear. Upstream stimulatory factor (USF) is a bHLH-ZIP protein which does not interact with members of the myc-max-mad family. By replacing the HLH-ZIP domain of max with that from USF, we created a chimeric protein, max(USF), which was indistinguishable from max with respect to its ability to homodimerize and bind DNA. As expected, however, max(USF) was unable to heterodimerize with any of the tested max partner proteins and was incapable of suppressing c-myc target genes. Thus, transcriptional repression is an exclusive property of max-mad heterodimers and cannot be achieved by max homodimers alone.
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh, Pennsylvania, USA.
authors.forename: X
authors.initials: X
authors.lastname: Yin
authors.forename: L
authors.initials: L
authors.lastname: Grove
authors.forename: E V
authors.initials: EV
authors.lastname: Prochownik
mesh_terms: D016475:3T3 Cells; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000235:genetics*; D019281:Dimerization; D005786:Gene Expression Regulation; D016259:Genes, myc; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D051720:Upstream Stimulatory Factors; D014764:Viral Proteins / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins; D015003:Yeasts / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C499479:Mad protein, mouse; C067850:Myc associated factor X; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; C068422:Max protein, mouse