An auxiliary peptide required for the function of two activation domains in upstream stimulatory factor 2 (USF2) transcription factor.
Ubiquitous upstream stimulatory factors (USF1, USF2a and USF2b) are members of the basic-helix-loop-helix-leucine-zipper family of transcription factors that have been shown to be involved in the transcriptional response of the L-type pyruvate kinase (L-PK) gene to glucose. To understand the mechanisms of action of the USF2 isoforms, we initiated a series of co-transfection assays with deletion mutants and Ga14-USF2 fusions. The transactivating efficiency of the different native and mutant factors was determined at similar DNA binding activity. We found that: (i) exons 3- and 5-encoded regions are activation domains, (ii) a modulator domain encoded by exon 4 could be necessary to their additive action, (iii) a hexapeptide encoded by the first 5' codons of exon 6 is indispensable for transmitting activation due to both exon 3- and exon 5-encoded domains to the transcriptional machinery. Therefore, USF2 presents a modular structure and mediates transcriptional activation thanks to two non-autonomous activation domains dependent on an auxiliary peptide for expressing their activating potential.
Gourdon
L
L
Unité de Recherches en Physiologie et Pathologie Génétiques et Moléculaires, Institut Cochin de Génétique Moléculaire, INSERM U129, Université René Descartes, Paris, France.
Lefrançois-Martinez
A M
AM
Viollet
B
B
Martinez
A
A
Kahn
A
A
Raymondjean
M
M
D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D051720:Upstream Stimulatory Factors
D017931:DNA Primers; D004268:DNA-Binding Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C497181:USF1 protein, human; C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors