Multiple cell-type-specific elements regulate Myc protein stability.
Myc is a highly unstable transcription factor that is destroyed by ubiquitin (Ub)-mediated proteolysis. We have previously identified an amino-terminal 'degron' within Myc that signals its destruction; this degron spans the transcriptional activation domain of Myc, and includes two highly conserved regions called Myc boxes I and II. We now report the identification of a second element--the D-element--which is also required for Myc proteolysis. The centrally located D-element is distinct from the PEST domain in Myc, but includes Myc box III, a third highly conserved region with no previously known function. We show that deletion of the D-element stabilizes the Myc protein without affecting its ubiquitylation, and report that the D-element and the degron act in a cell-type-specific manner to direct Myc proteolysis. These data thus demonstrate that Myc stability is regulated at both the ubiquitylation and postubiquitylation levels, and reveal that substrates of the Ub-proteasome system can be targeted for destruction differently in different cell types.
Herbst
Andreas
A
Cold Spring Harbor Laboratory, 1 Bungtown Rd, PO Box 100, Cold Spring Harbor, NY 11724, USA.
Salghetti
Simone E
SE
Kim
So Young
SY
Tansey
William P
WP
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D025801:Ubiquitin / Q000378:metabolism
D009097:Multienzyme Complexes; D016271:Proto-Oncogene Proteins c-myc; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex