THE C-TERMINAL DOMAIN OF MAD-LIKE SIGNAL TRANSDUCERS IS SUFFICIENT FOR BIOLOGICAL-ACTIVITY IN THE XENOPUS EMBRYO AND TRANSCRIPTIONAL ACTIVATION

We report the characterization of two vertebrate homologs of Drosophil a mothers against dpp (Mad) isolated from the mouse and the Xenopus em bryo, named MusMLP (mad-like protein) and XenMLP, respectively, togeth er with a summary of their expression patterns in the embryo. Overexpr ession of XenMLP causes ventralization of Xenopus embryos and we demon strate that the C-terminal domain is necessary and sufficient to confe r this biological effect. This domain also has the potential for trans criptional activation, as shown in one-hybrid assays in mammalian cell s. We further demonstrate that MLPs are multidomain proteins by showin g a cis-negative effect of the N-terminal domain on the transactivatio n by the C-terminal domain and that the proline-rich, middle domain ma ximizes the activity of the C-terminal domain. We also mapped the MusM LP gene to a region on mouse chromosome 13 that corresponds to a regio n on human chromosome 59 that contains cancer-related genes. (C) 1997 Elsevier Science Ireland Ltd.