Stable and unstable pools of Myc protein exist in human cells.
The oncoprotein transcription factor Myc plays a crucial role in the control of cell growth and proliferation. Consistent with its potent growth-promoting properties, cells have evolved a number of mechanisms to limit the activity and accumulation of the Myc protein. One of the most striking of these mechanisms is ubiquitin (Ub)-mediated proteolysis, which typically destroys Myc within minutes of its synthesis. Here we show that, despite the extreme instability of the Myc protein, cells contain a pool of Myc that is metabolically stable. Entry of Myc into the stable pool is signaled by an element within the carboxy-terminus of the protein, and is a cell-specific process that is regulated during mitosis and by interaction with Max. These data demonstrate that - even for a rapidly turned-over protein such as Myc - metabolically stable and unstable forms of a protein can co-exist in cells, and suggest that the rate of destruction of Myc molecules is linked to their specific functions.
Tworkowski
Kathryn A
KA
Molecular and Cellular Biology Program, State University of New York at Stony Brook, 11794, USA.
Salghetti
Simone E
SE
Tansey
William P
WP
D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D025801:Ubiquitin