Revealing the cellular degradome by mass spectrometry analysis of proteasome-cleaved peptides

Hila Wolf-Levy; Aaron Javitt; Avital Eisenberg-Lerner; Assaf Kacenl; Adi Ulman; Daoud Sheban; Bareket Dassa; Vered Fishbain-Yoskovitz; Carmelo Carmona-Rivera; Matthias P. Kramer; Neta Nudel; Ifat Regev; Liron Zahavi; Dalia Elinger; Mariana J. Kaplan; David Morgenstern; Yishai Levin; Yifat Merbl

doi:10.1038/nbt.4279

Revealing the cellular degradome by mass spectrometry analysis of proteasome-cleaved peptides

Hila Wolf-Levy, Aaron Javitt, Avital Eisenberg-Lerner, Assaf Kacenl, Adi Ulman, Daoud Sheban, Bareket Dassa, Vered Fishbain-Yoskovitz, Carmelo Carmona-Rivera, Matthias P. Kramer, Neta Nudel, Ifat Regev, Liron Zahavi, Dalia Elinger, Mariana J. Kaplan, David Morgenstern, Yishai Levin, Yifat Merbl

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

Abstract

Cellular function is critically regulated through degradation of substrates by the proteasome. To enable direct analysis of naturally cleaved proteasomal peptides under physiological conditions, we developed mass spectrometry analysis of proteolytic peptides (MAPP), a method for proteasomal footprinting that allows for capture, isolation and analysis of proteasome-cleaved peptides. Application of MAPP to cancer cell lines as well as primary immune cells revealed dynamic modulation of the cellular degradome in response to various stimuli, such as proinflammatory signals. Further, we performed analysis of minute amounts of clinical samples by studying cells from the peripheral blood of patients with systemic lupus erythematosus (SLE). We found increased degradation of histones in patient immune cells, thereby suggesting a role of aberrant proteasomal degradation in the pathophysiology of SLE. Thus, MAPP offers a broadly applicable method to facilitate the study of the cellular-degradation landscape in various cellular conditions and diseases involving changes in proteasomal degradation, including protein aggregation diseases, autoimmunity and cancer.

Original language	English
Pages (from-to)	1110-1116
Number of pages	7
Journal	Nature biotechnology
Volume	36
Issue number	11
DOIs	https://doi.org/10.1038/nbt.4279
State	Published - Nov 2018

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Wolf-Levy, H., Javitt, A., Eisenberg-Lerner, A., Kacenl, A., Ulman, A., Sheban, D., Dassa, B., Fishbain-Yoskovitz, V., Carmona-Rivera, C., Kramer, M. P., Nudel, N., Regev, I., Zahavi, L., Elinger, D., Kaplan, M. J., Morgenstern, D., Levin, Y., & Merbl, Y. (2018). Revealing the cellular degradome by mass spectrometry analysis of proteasome-cleaved peptides. Nature biotechnology, 36(11), 1110-1116. https://doi.org/10.1038/nbt.4279

@article{e896ab643a894eb8943403abb43e490d,

title = "Revealing the cellular degradome by mass spectrometry analysis of proteasome-cleaved peptides",

abstract = "Cellular function is critically regulated through degradation of substrates by the proteasome. To enable direct analysis of naturally cleaved proteasomal peptides under physiological conditions, we developed mass spectrometry analysis of proteolytic peptides (MAPP), a method for proteasomal footprinting that allows for capture, isolation and analysis of proteasome-cleaved peptides. Application of MAPP to cancer cell lines as well as primary immune cells revealed dynamic modulation of the cellular degradome in response to various stimuli, such as proinflammatory signals. Further, we performed analysis of minute amounts of clinical samples by studying cells from the peripheral blood of patients with systemic lupus erythematosus (SLE). We found increased degradation of histones in patient immune cells, thereby suggesting a role of aberrant proteasomal degradation in the pathophysiology of SLE. Thus, MAPP offers a broadly applicable method to facilitate the study of the cellular-degradation landscape in various cellular conditions and diseases involving changes in proteasomal degradation, including protein aggregation diseases, autoimmunity and cancer.",

author = "Hila Wolf-Levy and Aaron Javitt and Avital Eisenberg-Lerner and Assaf Kacenl and Adi Ulman and Daoud Sheban and Bareket Dassa and Vered Fishbain-Yoskovitz and Carmelo Carmona-Rivera and Kramer, {Matthias P.} and Neta Nudel and Ifat Regev and Liron Zahavi and Dalia Elinger and Kaplan, {Mariana J.} and David Morgenstern and Yishai Levin and Yifat Merbl",

year = "2018",

month = nov,

doi = "10.1038/nbt.4279",

language = "الإنجليزيّة",

volume = "36",

pages = "1110--1116",

journal = "Nature biotechnology",

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publisher = "Nature Research",

number = "11",

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Wolf-Levy, H, Javitt, A, Eisenberg-Lerner, A, Kacenl, A, Ulman, A, Sheban, D, Dassa, B, Fishbain-Yoskovitz, V, Carmona-Rivera, C, Kramer, MP, Nudel, N, Regev, I, Zahavi, L, Elinger, D, Kaplan, MJ, Morgenstern, D, Levin, Y & Merbl, Y 2018, 'Revealing the cellular degradome by mass spectrometry analysis of proteasome-cleaved peptides', Nature biotechnology, vol. 36, no. 11, pp. 1110-1116. https://doi.org/10.1038/nbt.4279

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T1 - Revealing the cellular degradome by mass spectrometry analysis of proteasome-cleaved peptides

AU - Wolf-Levy, Hila

AU - Javitt, Aaron

AU - Eisenberg-Lerner, Avital

AU - Kacenl, Assaf

AU - Ulman, Adi

AU - Sheban, Daoud

AU - Dassa, Bareket

AU - Fishbain-Yoskovitz, Vered

AU - Carmona-Rivera, Carmelo

AU - Kramer, Matthias P.

AU - Nudel, Neta

AU - Regev, Ifat

AU - Zahavi, Liron

AU - Elinger, Dalia

AU - Kaplan, Mariana J.

AU - Morgenstern, David

AU - Levin, Yishai

AU - Merbl, Yifat

PY - 2018/11

Y1 - 2018/11

N2 - Cellular function is critically regulated through degradation of substrates by the proteasome. To enable direct analysis of naturally cleaved proteasomal peptides under physiological conditions, we developed mass spectrometry analysis of proteolytic peptides (MAPP), a method for proteasomal footprinting that allows for capture, isolation and analysis of proteasome-cleaved peptides. Application of MAPP to cancer cell lines as well as primary immune cells revealed dynamic modulation of the cellular degradome in response to various stimuli, such as proinflammatory signals. Further, we performed analysis of minute amounts of clinical samples by studying cells from the peripheral blood of patients with systemic lupus erythematosus (SLE). We found increased degradation of histones in patient immune cells, thereby suggesting a role of aberrant proteasomal degradation in the pathophysiology of SLE. Thus, MAPP offers a broadly applicable method to facilitate the study of the cellular-degradation landscape in various cellular conditions and diseases involving changes in proteasomal degradation, including protein aggregation diseases, autoimmunity and cancer.

AB - Cellular function is critically regulated through degradation of substrates by the proteasome. To enable direct analysis of naturally cleaved proteasomal peptides under physiological conditions, we developed mass spectrometry analysis of proteolytic peptides (MAPP), a method for proteasomal footprinting that allows for capture, isolation and analysis of proteasome-cleaved peptides. Application of MAPP to cancer cell lines as well as primary immune cells revealed dynamic modulation of the cellular degradome in response to various stimuli, such as proinflammatory signals. Further, we performed analysis of minute amounts of clinical samples by studying cells from the peripheral blood of patients with systemic lupus erythematosus (SLE). We found increased degradation of histones in patient immune cells, thereby suggesting a role of aberrant proteasomal degradation in the pathophysiology of SLE. Thus, MAPP offers a broadly applicable method to facilitate the study of the cellular-degradation landscape in various cellular conditions and diseases involving changes in proteasomal degradation, including protein aggregation diseases, autoimmunity and cancer.

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DO - 10.1038/nbt.4279

M3 - مقالة

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VL - 36

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EP - 1116

JO - Nature biotechnology

JF - Nature biotechnology

IS - 11

ER -

Revealing the cellular degradome by mass spectrometry analysis of proteasome-cleaved peptides

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