The role of human MBF1 as a transcriptional coactivator.
Multiprotein bridging factor 1 (MBF1) is a coactivator which mediates transcriptional activation by interconnecting the general transcription factor TATA element-binding protein and gene-specific activators such as the Drosophila nuclear receptor FTZ-F1 or the yeast basic leucine zipper protein GCN4. The human homolog of MBF1 (hMBF1) has been identified but its function, especially in transcription, remains unclear. Here we report the cDNA cloning and functional analysis of hMBF1. Two isoforms, which we term hMBF1alpha and hMBF1beta, have been identified. hMBF1alpha mRNA was detected in a number of tissues, whereas hMBF1beta exhibited tissue-specific expression. Both isoforms bound to TBP and Ad4BP/SF-1, a mammalian counterpart of FTZ-F1, and mediated Ad4BP/SF-1-dependent transcriptional activation. While hMBF1 was detected in the cytoplasm by immunostaining, coexpression of the nuclear protein Ad4BP/SF-1 with hMBF1 induced accumulation of hMBF1 in the nucleus, suggesting that hMBF1 is localized in the nucleus through its binding to Ad4BP/SF-1. hMBF1 also bound to ATF1, a member of the basic leucine zipper protein family, and mediated its activity as a transcriptional activator. These data establish that the coactivator MBF1 is functionally conserved in eukaryotes.
Kabe
Y
Y
Faculty of Bioscience, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
Goto
M
M
Shima
D
D
Imai
T
T
Wada
T
T
Morohashi
K i
Ki
Shirakawa
M
M
Hirose
S
S
Handa
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D019556:COS Cells; D002148:Calmodulin-Binding Proteins; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D005455:Fluorescent Antibody Technique; D051717:Fushi Tarazu Transcription Factors; D015870:Gene Expression; D006367:HeLa Cells; D018398:Homeodomain Proteins; D006801:Humans; D016350:Leucine Zippers; D008297:Male; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D054339:Steroidogenic Factor 1; D035181:TATA-Box Binding Protein; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D002148:Calmodulin-Binding Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C115911:EDF1 protein, human; C485470:Edf1 protein, mouse; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C491465:MBF1 protein, Drosophila; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D054339:Steroidogenic Factor 1; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D014157:Transcription Factors