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Dynamics of the p53-Mdm2 feedback loop in individual cells

Lahav, Galit and Rosenfeld, Nitzan and Sigal, Alex and Geva-Zatorsky, Naama and Levine, Arnold J. and Elowitz, Michael B. and Alon, Uri (2004) Dynamics of the p53-Mdm2 feedback loop in individual cells. Nature Genetics, 36 (2). pp. 147-150. ISSN 1061-4036. doi:10.1038/ng1293.

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The tumor suppressor p53, one of the most intensely investigated proteins, is usually studied by experiments that are averaged over cell populations, potentially masking the dynamic behavior in individual cells. We present a system for following, in individual living cells, the dynamics of p53 and its negative regulator Mdm2 (refs. 1,4−7): this system uses functional p53-CFP and Mdm2-YFP fusion proteins and time-lapse fluorescence microscopy. We found that p53 was expressed in a series of discrete pulses after DNA damage. Genetically identical cells had different numbers of pulses: zero, one, two or more. The mean height and duration of each pulse were fixed and did not depend on the amount of DNA damage. The mean number of pulses, however, increased with DNA damage. This approach can be used to study other signaling systems and suggests that the p53-Mdm2 feedback loop generates a 'digital' clock that releases well-timed quanta of p53 until damage is repaired or the cell dies.

Item Type:Article
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URLURL TypeDescription ReadCube access
Sigal, Alex0000-0001-8571-2004
Elowitz, Michael B.0000-0002-1221-0967
Additional Information:© 2004 Nature Publishing Group. Received 21 September; accepted 15 December 2003. Published online: 18 January 2004. We thank M. Oren, D. Ginsberg and Z. Kam for help, reagents and discussions; L. Ben-Artzi and A. Lahav for assistance; and B. Geiger, Y. Liron, V. Rotter, C. Walsh and all members of our laboratory for discussions. We acknowledge support from the ISF, Minerva, Abisch-Frenkel, Harry M. Ringel and Mr. and Mrs. Mordechai Segal foundations and a David Aftalion postdoctoral fellowship to G.L. This work is dedicated to the memory of Yasha (Yaakov) Rosenfeld.
Funding AgencyGrant Number
Israel Science FoundationUNSPECIFIED
Harry M. Ringel FoundationUNSPECIFIED
Mr. and Mrs. Mordechai Segal FoundationUNSPECIFIED
David Aftalion postdoctoral fellowshipUNSPECIFIED
Issue or Number:2
Record Number:CaltechAUTHORS:20150408-095048891
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ID Code:56468
Deposited By: Ruth Sustaita
Deposited On:08 Apr 2015 17:06
Last Modified:10 Nov 2021 20:59

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