MYC BOXES, WHICH ARE CONSERVED IN MYC FAMILY PROTEINS, ARE SIGNALS FOR PROTEIN-DEGRADATION VIA THE PROTEASOME

Cellular levels of the rapidly degraded c-myc protein play an importan t role in determining the proliferation status of cells. Increased lev els of c-myc are frequently associated with rapidly proliferating tumo r cells. We show here that myc boxes I and II, found in the N termini of all members of the myc protein family, function to direct the degra dation of the c-myc protein. Both myc boxes I and II contain sufficien t information to independently direct the degradation of otherwise sta bly expressed proteins to which they are fused. At least part of the m yc box-directed degradation occurs via the proteasome. The mechanism o f myc box-directed degradation appears to be conserved between yeast a nd mammalian cells. Our results suggest that the myc boxes may play an important role in regulating the level and activity of the c-myc prot ein.