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Multiprotein Bridging Factor-1 (MBF-1) Is a Cofactor for Nuclear Receptors that Regulate Lipid Metabolism

Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre Nationale de la Recherche Scientifique/INSERM/Université Louis Pasteur, BP 163, 67404 Illkirch, France

Address all correspondence and reprint requests to: Dr. Johan Auwerx, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Parc d’Innovation, 1 rue Laurent Fries, 67404 Illkirch, France. E-mail: auwerx{at}igbmc.u-strasbg.fr.

Multiprotein bridging factor (MBF-1) is a cofactor that was first described for its capacity to modulate the activity of fushi tarazu factor 1, a nuclear receptor originally implicated in Drosophila development. Recently, it has been shown that human MBF-1 stimulates the transcriptional activity of steroidogenic factor 1, a human homolog of fushi tarazu factor 1, which is implicated in steroidogenesis. Here we show that this cofactor enhances the transcriptional activity of several nonsteroid nuclear receptors that are implicated in lipid metabolism, i.e. the liver receptor homolog 1, the liver X receptor , and PPAR. MBF-1 interacts with distinct domains in these receptors, depending on whether the receptor binds DNA as a monomer or as a heterodimer with RXR. MBF-1 does not possess any of the classical histone modifying activities such as histone acetyl- or methyl transferase activities, linked to chromatin remodeling, but interacts in vitro with the transcription factor IID complex. MBF-1 seems therefore to act as a bridging factor enabling interactions of nuclear receptors with the transcription machinery.

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