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.
Unité de Recherches en Physiologie et Pathologie Génétiques et Moléculaires, Institut Cochin de Génétique Moléculaire, INSERM U129, Université René Descartes, Paris, France.
L
L
Gourdon
A M
AM
Lefrançois-Martinez
B
B
Viollet
A
A
Martinez
A
A
Kahn
M
M
Raymondjean
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