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 important role in determining the proliferation status of cells. Increased levels of c-myc are frequently associated with rapidly proliferating tumor 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 degradation of the c-myc protein. Both myc boxes I and II contain sufficient information to independently direct the degradation of otherwise stably expressed proteins to which they are fused. At least part of the myc box-directed degradation occurs via the proteasome. The mechanism of myc box-directed degradation appears to be conserved between yeast and mammalian cells. Our results suggest that the myc boxes may play an important role in regulating the level and activity of the c-myc protein.
Flinn
E M
EM
Karolinska Institute, Department of Biosciences, NOVUM, S-14157 Huddinge, Sweden. elizabeth.flinn@cbt.ki.se
Busch
C M
CM
Wright
A P
AP
D000818:Animals; D019556:COS Cells; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism
D009097:Multienzyme Complexes; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex