Cross-family interaction between the bHLHZip USF and bZip Fra1 proteins results in down-regulation of AP1 activity.
Heterodimerization among the basic-leucine zipper (bZIP) proteins or among the basic-helix-loop-helix-leucine zipper (bHLHZip) proteins confers a multitude of combinational activities to these transcription factors. To further examine the function of the bHLHZip protein, USF, we screened for cellular proteins which could directly interact with USF using the yeast two-hybrid system. A bZip protein, Fra1, was found to efficiently interact with USF. USF specifically interacts with Fra1 but not with other closely related family members, c-Fos, Fra2, FosB, or with c-Jun. Both the bHLHZip and the N-terminal regions of Fra1 are required for efficient interaction with USF. In vivo association between USF and Fra1 has been demonstrated by co-immunoprecipitation. Expression of exogenous USF led to a decrease in AP1-dependent transcription in F9 cells. Co-expression of exogenous Fra1 restored the AP1 activity in a dose-dependent manner. These data show that USF and Fra1 physically and functionally interact demonstrating that cross-talk occurs between factors of distantly related transcription families.
Pognonec
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P
Centre de Biochimie, Universite de Nice, France.
Boulukos
K E
KE
Aperlo
C
C
Fujimoto
M
M
Ariga
H
H
Nomoto
A
A
Kato
H
H
D000818:Animals; D004268:DNA-Binding Proteins; D019281:Dimerization; D017930:Genes, Reporter; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D016350:Leucine Zippers; D051379:Mice; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors; D001616:beta-Galactosidase / Q000096:biosynthesis; D000099169:Fos-Related Antigen 1
D004268:DNA-Binding Proteins; D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D001616:beta-Galactosidase; D000099169:Fos-Related Antigen 1; C497181:USF1 protein, human; C497183:Usf1 protein, mouse