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Science 331 (6018): 764-768

Copyright © 2011 by the American Association for the Advancement of Science

Proteome Half-Life Dynamics in Living Human Cells

Eran Eden,*,{dagger} Naama Geva-Zatorsky,* Irina Issaeva, Ariel Cohen, Erez Dekel, Tamar Danon, Lydia Cohen, Avi Mayo, Uri Alon{dagger}

Abstract: Cells remove proteins by two processes: degradation and dilution due to cell growth. The balance between these basic processes is poorly understood. We addressed this by developing an accurate and noninvasive method for measuring protein half-lives, called "bleach-chase," that is applicable to fluorescently tagged proteins. Assaying 100 proteins in living human cancer cells showed half-lives that ranged between 45 minutes and 22.5 hours. A variety of stresses that stop cell division showed the same general effect: Long-lived proteins became longer-lived, whereas short-lived proteins remained largely unaffected. This effect is due to the relative strengths of degradation and dilution and suggests a mechanism for differential killing of rapidly growing cells by growth-arresting drugs. This approach opens a way to understand proteome half-life dynamics in living cells.

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: eraneden{at}gmail.com (E.E.); urialon{at}weizmann.ac.il (U.A.)

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