September 2005

Opening the O-box

Dr. Maki Asano and colleagues have discovered a novel protein motif that regulates Drosophila cell cycle progression by targeting the origin recognition complex (ORC1) for degradation by the ubiquitin ligase, APC. The ORC destruction box, or the "O-box" as is it called, may serve a more widespread role in the proteosomal degradation of various cell cycle factors in other eukaryotes, as well. This work reveals a heretofore unknown mechanism for the degradation of Drosophila ORC1 by the APC at the end of the M phase of the cell cycle, as well as adding to the short list of previously identified APC targeting motifs (the A-, D-, KEN-, and GXEN-boxes). Further work will be aimed at elucidating the relationship between the O-box and the other destruction sequences in the regulation of proteolysis. Dr. Asano adds that "This work identifies a new signal that flags protein for degradation and we are looking forward to finding additional O-box proteins that may play roles in cell cycle control."