The Role of Human MBF1 as a Transcriptional Coactivator

Abstract

Multiprotein bridging factor 1 (MBF1) is a coactivator which mediates transcriptional activation by interconnecting the general transcription factor TATA elementbinding 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 hMBF1␣ and hMBF1␤, have been identified. hMBF1␣ mRNA was detected in a number of tissues, whereas hMBF1␤ 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.

Differential expression and interaction of transcription co-activator MBF1 with TATA-binding protein (TBP) in the apicomplexan Cryptosporidium parvum

“…The CpMBF1 transcription level is low in free sporozoites and intracellular parasites during their early invasion stages, and CpMBF1 protein is barely detectable in intact oocysts and free sporozoites, suggesting that CpMBF1 may play a role in activating certain genes during the intracellular development of C. parvum. In addition to the activation of histidine synthetic genes in yeast under histidine starvation, MBF1-mediated pathways are known to cause cell differentiation in insects, the formation of stalks in the slime mould Dictyostelium discoideum and the differentiation of endothelial cells in mammals (Dragoni et al, 1998;Kabe et al, 1999;Singleton et al, 1991;Takemaru et al, 1997). These observations, together with the parasite life cycle stage-dependent expression pattern, imply that CpMBF1 may be involved in the cell differentiation of C. parvum during its complex life cycle.…”

“…Drosophila nuclear receptor FTZ-F1 or yeast leucine zipper protein GCN4) (Dragoni et al, 1998;Kabe et al, 1999;Li et al, 1994;Liu et al, 2003;Takemaru et al, 1997Takemaru et al, , 1998. We have previously identified its C. parvum counterpart and demonstrated that the CpMBF1 gene is able to functionally complement MBF1 deficiency in yeast (Zhu et al, 2000).…”

“…Multiprotein bridging factor type 1 (MBF1) was first identified in Drosophila as a mediator of the transcriptional activator FTZ-F1 and found to be evolutionarily conserved among a wide range of eukaryotic organisms including humans, animals, plants, insects, fungi and protists (Kabe et al, 1999;Liu et al, 2003;Takemaru et al, 1997Takemaru et al, , 1998Zhu et al, 2000). MBF1 acts as a transcriptional co-activator that recruits DNA-binding regulators and TATA-binding protein (TBP) for the conditional or differential activation of gene expression.…”

Homeodomain-leucine Zipper Proteins Interact with a Plant Homologue of the Transcriptional Co-activator Multiprotein Bridging Factor 1

“…Later, the MBF1 homologues factors were identified in yeast, parasites, and humans (Takemaru et al, 1997;Kabe et al, 1999;Zhu et al, 2000). Takemaru et al (1997) and Kabe et al (1999) found that yeast and human MBF1 bind to different transcription factors of the basic leucine zipper (bZip) family, including yeast GCN4, bovine Ad4BP/SF1, and human ATF1, c-Jun, and c-Fos. Godoy et al, (2001) isolated and characterized a potato (Solanum tuberosum) cDNA clone that encodes a protein (StMBF1) with high sequence homology with human, yeast, and Bombix mori MBF1.…”

“…The multiprotein bridging factor 1 (MBF1) was originally purified from extracts of the silkworm Bombyx mori and identified as a transcriptional co-activator that interacts with the general transcription factor TBP (TATA box binding protein) and the Drosophila melanogaster nuclear receptor FTZ-F1 (Li et al, 1994). Later, the MBF1 homologues factors were identified in yeast, parasites, and humans (Takemaru et al, 1997;Kabe et al, 1999;Zhu et al, 2000). Takemaru et al (1997) and Kabe et al (1999) found that yeast and human MBF1 bind to different transcription factors of the basic leucine zipper (bZip) family, including yeast GCN4, bovine Ad4BP/SF1, and human ATF1, c-Jun, and c-Fos.…”