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Science 322 (5903): 918-923

Copyright © 2008 by the American Association for the Advancement of Science

Global Protein Stability Profiling in Mammalian Cells

Hsueh-Chi Sherry Yen, Qikai Xu,* Danny M. Chou,* Zhenming Zhao, Stephen J. Elledge{dagger}

Abstract: The abundance of cellular proteins is determined largely by the rate of transcription and translation coupled with the stability of individual proteins. Although we know a great deal about global transcript abundance, little is known about global protein stability. We present a highly parallel multiplexing strategy to monitor protein turnover on a global scale by coupling flow cytometry with microarray technology to track the stability of individual proteins within a complex mixture. We demonstrated the feasibility of this approach by measuring the stability of ~8000 human proteins and identifying proteasome substrates. The technology provides a general platform for proteome-scale analysis of protein turnover under various physiological and disease conditions.

Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: selledge{at}

A global view of protein expression in human cells, tissues, and organs.
F. Ponten, M. Gry, L. Fagerberg, E. Lundberg, A. Asplund, L. Berglund, P. Oksvold, E. Bjorling, S. Hober, C. Kampf, et al. (2014)
Mol Syst Biol 5, 337
   Abstract »    Full Text »    PDF »
Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line.
C. Vogel, R. de Sousa Abreu, D. Ko, S.-Y. Le, B. A. Shapiro, S. C. Burns, D. Sandhu, D. R. Boutz, E. M. Marcotte, and L. O. Penalva (2014)
Mol Syst Biol 6, 400
   Abstract »    Full Text »    PDF »
Dynamics of protein noise can distinguish between alternate sources of gene-expression variability.
A. Singh, B. S. Razooky, R. D. Dar, and L. S. Weinberger (2014)
Mol Syst Biol 8, 607
   Abstract »    Full Text »    PDF »
Protein synthesis rate is the predominant regulator of protein expression during differentiation.
A. R. Kristensen, J. Gsponer, and L. J. Foster (2014)
Mol Syst Biol 9, 689
   Abstract »    Full Text »    PDF »
An in vivo control map for the eukaryotic mRNA translation machinery.
H. Firczuk, S. Kannambath, J. Pahle, A. Claydon, R. Beynon, J. Duncan, H. Westerhoff, P. Mendes, and J. E. McCarthy (2014)
Mol Syst Biol 9, 635
   Abstract »    Full Text »    PDF »
Occurrence of protein disulfide bonds in different domains of life: a comparison of proteins from the Protein Data Bank.
I. Bosnjak, V. Bojovic, T. Segvic-Bubic, and A. Bielen (2014)
Protein Eng. Des. Sel. 27, 65-72
   Abstract »    Full Text »    PDF »
The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins.
G. Lu, R. E. Middleton, H. Sun, M. Naniong, C. J. Ott, C. S. Mitsiades, K.-K. Wong, J. E. Bradner, and W. G. Kaelin Jr. (2014)
Science 343, 305-309
   Abstract »    Full Text »    PDF »
A C-Terminal Acidic Domain Regulates Degradation of the Transcriptional Coactivator Bob1.
J. M. Lindner, C. S. F. Wong, A. Moller, and P. J. Nielsen (2013)
Mol. Cell. Biol. 33, 4628-4640
   Abstract »    Full Text »    PDF »
A High-Throughput-Compatible 3D Microtissue Co-Culture System for Phenotypic RNAi Screening Applications.
C. R. Thoma, S. Stroebel, N. Rosch, B. Calpe, W. Krek, and J. M. Kelm (2013)
J Biomol Screen 18, 1330-1337
   Abstract »    Full Text »    PDF »
Using the Ubiquitin-modified Proteome to Monitor Protein Homeostasis Function.
A. C. Carrano and E. J. Bennett (2013)
Mol. Cell. Proteomics 12, 3521-3531
   Abstract »    Full Text »    PDF »
Pseudogenes and their composers: delving in the 'debris' of human genome.
K. Sen and T. C. Ghosh (2013)
Briefings in Functional Genomics 12, 536-547
   Abstract »    Full Text »    PDF »
High-throughput Analysis of in vivo Protein Stability.
I. Kim, C. R. Miller, D. L. Young, and S. Fields (2013)
Mol. Cell. Proteomics 12, 3370-3378
   Abstract »    Full Text »    PDF »
Global Subcellular Characterization of Protein Degradation Using Quantitative Proteomics.
M. Larance, Y. Ahmad, K. J. Kirkwood, T. Ly, and A. I. Lamond (2013)
Mol. Cell. Proteomics 12, 638-650
   Abstract »    Full Text »    PDF »
Quantitative profiling of caspase-cleaved substrates reveals different drug-induced and cell-type patterns in apoptosis.
K. Shimbo, G. W. Hsu, H. Nguyen, S. Mahrus, J. C. Trinidad, A. L. Burlingame, and J. A. Wells (2012)
PNAS 109, 12432-12437
   Abstract »    Full Text »    PDF »
Differential Diffusivity of Nodal and Lefty Underlies a Reaction-Diffusion Patterning System.
P. Muller, K. W. Rogers, B. M. Jordan, J. S. Lee, D. Robson, S. Ramanathan, and A. F. Schier (2012)
Science 336, 721-724
   Abstract »    Full Text »    PDF »
A Quantitative Spatial Proteomics Analysis of Proteome Turnover in Human Cells.
F.-M. Boisvert, Y. Ahmad, M. Gierlinski, F. Charriere, D. Lamont, M. Scott, G. Barton, and A. I. Lamond (2012)
Mol. Cell. Proteomics 11, M111.011429
   Abstract »    Full Text »    PDF »
Mechanism of CRL4Cdt2, a PCNA-dependent E3 ubiquitin ligase.
C. G. Havens and J. C. Walter (2011)
Genes & Dev. 25, 1568-1582
   Abstract »    Full Text »    PDF »
Mitochondrial protein turnover: role of the precursor intermediate peptidase Oct1 in protein stabilization.
F.- N. Vogtle, C. Prinz, J. Kellermann, F. Lottspeich, N. Pfanner, and C. Meisinger (2011)
Mol. Biol. Cell 22, 2135-2143
   Abstract »    Full Text »    PDF »
Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate.
M. J. Emanuele, A. Ciccia, A. E. H. Elia, and S. J. Elledge (2011)
PNAS 108, 9845-9850
   Abstract »    Full Text »    PDF »
The Lives of Proteins.
J. B. Plotkin (2011)
Science 331, 683-684
   Abstract »    Full Text »    PDF »
Proteome Half-Life Dynamics in Living Human Cells.
E. Eden, N. Geva-Zatorsky, I. Issaeva, A. Cohen, E. Dekel, T. Danon, L. Cohen, A. Mayo, and U. Alon (2011)
Science 331, 764-768
   Abstract »    Full Text »    PDF »
Quantitative Protein and mRNA Profiling Shows Selective Post-Transcriptional Control of Protein Expression by Vasopressin in Kidney Cells.
S. Khositseth, T. Pisitkun, D. H. Slentz, G. Wang, J. D. Hoffert, M. A. Knepper, and M.-J. Yu (2011)
Mol. Cell. Proteomics 10, M110.004036
   Abstract »    Full Text »    PDF »
Ubiquitin accumulation in autophagy-deficient mice is dependent on the Nrf2-mediated stress response pathway: a potential role for protein aggregation in autophagic substrate selection.
B. E. Riley, S. E. Kaiser, T. A. Shaler, A. C. Y. Ng, T. Hara, M. S. Hipp, K. Lage, R. J. Xavier, K.-Y. Ryu, K. Taguchi, et al. (2010)
J. Cell Biol. 191, 537-552
   Abstract »    Full Text »    PDF »
Evolutionarily Conserved Role of Calcineurin in Phosphodegron-Dependent Degradation of Phosphodiesterase 4D.
H. Zhu, H. Y. Suk, R. Y. L. Yu, D. Brancho, O. Olabisi, T. T. C. Yang, X. Yang, J. Zhang, M. Moussaif, J. L. Durand, et al. (2010)
Mol. Cell. Biol. 30, 4379-4390
   Abstract »    Full Text »    PDF »
Temperature-sensitive Post-translational Regulation of Plant Omega-3 Fatty-acid Desaturases Is Mediated by the Endoplasmic Reticulum-associated Degradation Pathway.
J. B. O'Quin, L. Bourassa, D. Zhang, J. M. Shockey, S. K. Gidda, S. Fosnot, K. D. Chapman, R. T. Mullen, and J. M. Dyer (2010)
J. Biol. Chem. 285, 21781-21796
   Abstract »    Full Text »    PDF »
Small RING Finger Proteins RBX1 and RBX2 of SCF E3 Ubiquitin Ligases: The Role in Cancer and as Cancer Targets.
D. Wei and Y. Sun (2010)
Genes & Cancer 1, 700-707
   Abstract »    Full Text »    PDF »
Folding Study of Venus Reveals a Strong Ion Dependence of Its Yellow Fluorescence under Mildly Acidic Conditions.
S.-T. D. Hsu, G. Blaser, C. Behrens, L. D. Cabrita, C. M. Dobson, and S. E. Jackson (2010)
J. Biol. Chem. 285, 4859-4869
   Abstract »    Full Text »    PDF »
Synthetic design of strong promoters.
M. R. Schlabach, J. K. Hu, M. Li, and S. J. Elledge (2010)
PNAS 107, 2538-2543
   Abstract »    Full Text »    PDF »
Defective Ribosomal Products Are the Major Source of Antigenic Peptides Endogenously Generated from Influenza A Virus Neuraminidase.
B. P. Dolan, L. Li, K. Takeda, J. R. Bennink, and J. W. Yewdell (2010)
J. Immunol. 184, 1419-1424
   Abstract »    Full Text »    PDF »
Validation of SAG/RBX2/ROC2 E3 Ubiquitin Ligase as an Anticancer and Radiosensitizing Target.
L. Jia, J. Yang, X. Hao, M. Zheng, H. He, X. Xiong, L. Xu, and Y. Sun (2010)
Clin. Cancer Res. 16, 814-824
   Abstract »    Full Text »    PDF »
Recombination-induced tag exchange to track old and new proteins.
K. F. Verzijlbergen, V. Menendez-Benito, T. van Welsem, S. J. van Deventer, D. L. Lindstrom, H. Ovaa, J. Neefjes, D. E. Gottschling, and F. van Leeuwen (2010)
PNAS 107, 64-68
   Abstract »    Full Text »    PDF »
Aberrant DNA Polymerase {alpha} Is Excluded from the Nucleus by Defective Import and Degradation in the Nucleus.
C. S. Eichinger, T. Mizuno, K. Mizuno, Y. Miyake, K.-i. Yanagi, N. Imamoto, and F. Hanaoka (2009)
J. Biol. Chem. 284, 30604-30614
   Abstract »    Full Text »    PDF »
Cotranslational Proteolysis Dominates Glutathione Homeostasis to Support Proper Growth and Development.
F. Frottin, C. Espagne, J. A. Traverso, C. Mauve, B. Valot, C. Lelarge-Trouverie, M. Zivy, G. Noctor, T. Meinnel, and C. Giglione (2009)
PLANT CELL 21, 3296-3314
   Abstract »    Full Text »    PDF »
Hypoxia-inducible Factor Prolyl-4-hydroxylase PHD2 Protein Abundance Depends on Integral Membrane Anchoring of FKBP38.
S. Barth, F. Edlich, U. Berchner-Pfannschmidt, S. Gneuss, G. Jahreis, P. A. Hasgall, J. Fandrey, R. H. Wenger, and G. Camenisch (2009)
J. Biol. Chem. 284, 23046-23058
   Abstract »    Full Text »    PDF »
Analysis of Post-transcriptional Regulations by a Functional, Integrated, and Quantitative Method.
B. Laloo, D. Simon, V. Veillat, D. Lauzel, V. Guyonnet-Duperat, F. Moreau-Gaudry, F. Sagliocco, and C. Grosset (2009)
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   Abstract »    Full Text »    PDF »
ROC1/RBX1 E3 Ubiquitin Ligase Silencing Suppresses Tumor Cell Growth via Sequential Induction of G2-M Arrest, Apoptosis, and Senescence.
L. Jia, M. S. Soengas, and Y. Sun (2009)
Cancer Res. 69, 4974-4982
   Abstract »    Full Text »    PDF »
CELL BIOLOGY: Going Global on Ubiquitin.
C. Grabbe and I. Dikic (2008)
Science 322, 872-873
   Abstract »    Full Text »    PDF »
Identification of SCF Ubiquitin Ligase Substrates by Global Protein Stability Profiling.
H.-C. S. Yen and S. J. Elledge (2008)
Science 322, 923-929
   Abstract »    Full Text »    PDF »

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