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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.

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For reagents we thank C Bautista, D Bohmann, M Eilers, W Herr, N Hernandez and R Whittaker. We thank A Herbst, S Kim, Y Lazebnik, M Muratani and S Muthuswamy for discussions and critical comments on the manuscript. WP Tansey is a Leukemia and Lymphoma Society of America Scholar. KA Tworkowski is supported by training grant NIGMS-NIH 1T32-GM08468. This work was supported by the CSHL Cancer Center Support Grant CA45508 and by US Public Health Service grant CA-13106 from the National Cancer Institute.

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Correspondence to William P Tansey.

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Tworkowski, K., Salghetti, S. & Tansey, W. Stable and unstable pools of Myc protein exist in human cells. Oncogene 21, 8515–8520 (2002).

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  • Myc
  • Max
  • ubiquitin-mediated proteolysis

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