The role of human MBF1 as a transcriptional coactivator

Multiprotein bridging factor 1 (MBF1) is a coactivator which mediates trans criptional activation by interconnecting the general transcription factor T ATA element-binding protein and gene-specific activators such as the Drosop hila nuclear receptor FTZ-F1 or the yeast basic leucine zipper protein GCN4 , The human homolog of MBF1 (hMBF1) has been identified but its function, e specially in transcription, remains unclear. Here we report the cDNA clonin g and functional analysis of hMBF1. Two isoforms, which we term hMBF1 alpha and hMBF1 beta, have been identified. hMBF1 alpha mRNA was detected in a n umber of tissues, whereas hMBF1 beta exhibited tissue-specific expression. Both isoforms bound to TBP and Ad4BP/SF-1, a mammalian counterpart of FTZ-F 1, and mediated Ad4BP/SF-1-dependent transcriptional activation. While hMBF 1 was detected in the cytoplasm by immunostaining, coexpression of the nucl ear protein Ad4BP/SF-1 with hMBF1 induced accumulation of hMBF1 in the nucl eus, 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 zipp er protein family, and mediated its activity as a transcriptional activator . These data establish that the coactivator MBF1 is functionally conserved in eukaryotes.