Projects per year
MrfA, a transcription factor that regulates Dictyostelium prestalk cell differentiation, is an orthologue of the animal Myelin-gene Regulatory Factor (MRF) proteins. We show that the MRFs contain a predicted trans-membrane domain, suggesting that they are synthesized as membrane-tethered proteins that are then proteolytically released. We confirm this for MrfA but report a radically different mode of processing from that of paradigmatic tethered transcriptional regulators; which are cleaved within the trans-membrane domain by a dedicated protease. Instead an auto-proteolytic cleavage mechanism, previously only described for the intramolecular chaperone domains of bacteriophage tail-spike proteins, processes MrfA and, by implication, the metazoan MRF proteins. We also present evidence that the auto-proteolysis of MrfA occurs rapidly and constitutively in the ER and that its specific role in prestalk cell differentiation is conferred by the regulated nuclear translocation of the liberated fragment.
Aref#d: 19404. Delineation of the Signalling Pathways that Direct Cellular Differentiation in Dictyostelium (Principal Research Fellowship)
1/08/08 → 31/07/14