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Quantitative proteomics to decipher ubiquitin signaling

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Abstract

Ubiquitin signaling plays an essential role in controlling cellular processes in eukaryotes, and the impairment of ubiquitin regulation contributes to the pathogenesis of a wide range of human diseases. During the last decade, mass spectrometry-based proteomics has emerged as an indispensable approach for identifying the ubiquitinated proteome (ubiquitinome), ubiquitin modification sites, the linkages of complex ubiquitin chains, as well as the interactome of ubiquitin enzymes. In particular, implementation of quantitative strategies allows the detection of dynamic changes in the ubiquitinome, enhancing the ability to differentiate between function-relevant protein targets and false positives arising from biological and experimental variations. The profiling of total cell lysate and the ubiquitinated proteome in the same sets of samples has become a powerful tool, revealing a subset of substrates that are modulated by specific physiological and pathological conditions, such as gene mutations in ubiquitin signaling. This strategy is equally useful for dissecting the pathways of ubiquitin-like proteins.

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Acknowledgments

This work was partially supported by National Institutes of Health grant RR025822 and American Cancer Society grant RSG-09-181 and ALSAC (American Lebanese Syrian Associated Charities). We thank Joseph Mertz, and Drs. Zhiping Wu and Vani Shanker for critical reading and editing.

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Authors and Affiliations

  1. Departments of Structural Biology and Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, USA

    Ping-Chung Chen, Chan Hyun Na & Junmin Peng

  2. St. Jude Proteomics Facility, St. Jude Children’s Research Hospital, Memphis, TN, 38105, USA

    Junmin Peng

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  1. Ping-Chung Chen
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  2. Chan Hyun Na
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  3. Junmin Peng
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Correspondence to Junmin Peng.

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Chen, PC., Na, C.H. & Peng, J. Quantitative proteomics to decipher ubiquitin signaling. Amino Acids 43, 1049–1060 (2012). https://doi.org/10.1007/s00726-012-1286-y

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