PHR proteins are large conserved ubiquitin E3 ligases that have recently been shown to regulate a number of important steps during the development of the nervous system. Loss of function in the invertebrate PHR proteins, namely Drosophila Highwire and Caenorhabditis elegans RPM-1, results in dysregulation of synapse morphology, synapse growth, and axonal termination. Similar but more diverse effects have recently reported for the vertebrate PHR proteins. PHR proteins negatively regulate a conserved MAP kinase through ubiquitin-mediated protein degradation. They may also be involved in a wide range of signal transduction pathways involving cAMP, TSC, and BMP.
