DNA damage-induced dynamic changes in abundance and cytosol-nuclear translocation of proteins involved in translational processes, metabolism, and autophagy

Martin V. Bennetzen; Martin Kosar; Jakob Bunkenborg; Mark Ronald Payne; Jirina Bartkova; Mikael S Lindström; Jiri Lukas; Jens S. Andersen; Jiri Bartek; Dorthe Helena Larsen

doi:10.1080/15384101.2018.1515552

DNA damage-induced dynamic changes in abundance and cytosol-nuclear translocation of proteins involved in translational processes, metabolism, and autophagy

Martin V. Bennetzen, Martin Kosar, Jakob Bunkenborg, Mark Ronald Payne, Jirina Bartkova, Mikael S Lindström, Jiri Lukas, Jens S. Andersen, Jiri Bartek, Dorthe Helena Larsen

3 Citationer (Scopus)

Abstract

Ionizing radiation (IR) causes DNA double-strand breaks (DSBs) and activates a versatile cellular response regulating DNA repair, cell-cycle progression, transcription, DNA replication and other processes. In recent years proteomics has emerged as a powerful tool deepening our understanding of this multifaceted response. In this study we use SILAC-based proteomics to specifically investigate dynamic changes in cytoplasmic protein abundance after ionizing radiation; we present in-depth bioinformatics analysis and show that levels of proteins involved in autophagy (cathepsins and other lysosomal proteins), proteasomal degradation (Ubiquitin-related proteins), energy metabolism (mitochondrial proteins) and particularly translation (ribosomal proteins and translation factors) are regulated after cellular exposure to ionizing radiation. Downregulation of no less than 68 ribosomal proteins shows rapid changes in the translation pattern after IR. Additionally, we provide evidence of compartmental cytosol-nuclear translocation of numerous DNA damage related proteins using protein correlation profiling. In conclusion, these results highlight unexpected cytoplasmic processes actively orchestrated after genotoxic insults and protein translocation from the cytoplasm to the nucleus as a fundamental regulatory mechanism employed to aid cell survival and preservation of genome integrity.

Originalsprog	Engelsk
Tidsskrift	Cell Cycle
Vol/bind	17
Udgave nummer	17
Sider (fra-til)	2146-2163
ISSN	1538-4101
DOI	https://doi.org/10.1080/15384101.2018.1515552
Status	Udgivet - 2 sep. 2018

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10.1080/15384101.2018.1515552

15384101.2018.1515552?needAccess=trueForlagets udgivne version, 4,15 MB

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Bennetzen, M. V., Kosar, M., Bunkenborg, J., Payne, M. R., Bartkova, J., Lindström, M. S., Lukas, J., Andersen, J. S., Bartek, J., & Larsen, D. H. (2018). DNA damage-induced dynamic changes in abundance and cytosol-nuclear translocation of proteins involved in translational processes, metabolism, and autophagy. Cell Cycle, 17(17), 2146-2163. https://doi.org/10.1080/15384101.2018.1515552

Bennetzen, MV, Kosar, M, Bunkenborg, J, Payne, MR, Bartkova, J, Lindström, MS, Lukas, J, Andersen, JS, Bartek, J & Larsen, DH 2018, 'DNA damage-induced dynamic changes in abundance and cytosol-nuclear translocation of proteins involved in translational processes, metabolism, and autophagy', Cell Cycle, bind 17, nr. 17, s. 2146-2163. https://doi.org/10.1080/15384101.2018.1515552

@article{e9b2331d861b46e5a6e0671e0e34815b,

title = "DNA damage-induced dynamic changes in abundance and cytosol-nuclear translocation of proteins involved in translational processes, metabolism, and autophagy",

abstract = "Ionizing radiation (IR) causes DNA double-strand breaks (DSBs) and activates a versatile cellular response regulating DNA repair, cell-cycle progression, transcription, DNA replication and other processes. In recent years proteomics has emerged as a powerful tool deepening our understanding of this multifaceted response. In this study we use SILAC-based proteomics to specifically investigate dynamic changes in cytoplasmic protein abundance after ionizing radiation; we present in-depth bioinformatics analysis and show that levels of proteins involved in autophagy (cathepsins and other lysosomal proteins), proteasomal degradation (Ubiquitin-related proteins), energy metabolism (mitochondrial proteins) and particularly translation (ribosomal proteins and translation factors) are regulated after cellular exposure to ionizing radiation. Downregulation of no less than 68 ribosomal proteins shows rapid changes in the translation pattern after IR. Additionally, we provide evidence of compartmental cytosol-nuclear translocation of numerous DNA damage related proteins using protein correlation profiling. In conclusion, these results highlight unexpected cytoplasmic processes actively orchestrated after genotoxic insults and protein translocation from the cytoplasm to the nucleus as a fundamental regulatory mechanism employed to aid cell survival and preservation of genome integrity.",

author = "Bennetzen, {Martin V.} and Martin Kosar and Jakob Bunkenborg and Payne, {Mark Ronald} and Jirina Bartkova and Lindstr{\"o}m, {Mikael S} and Jiri Lukas and Andersen, {Jens S.} and Jiri Bartek and Larsen, {Dorthe Helena}",

year = "2018",

month = sep,

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doi = "10.1080/15384101.2018.1515552",

language = "English",

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journal = "Cell Cycle",

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TY - JOUR

T1 - DNA damage-induced dynamic changes in abundance and cytosol-nuclear translocation of proteins involved in translational processes, metabolism, and autophagy

AU - Bennetzen, Martin V.

AU - Kosar, Martin

AU - Bunkenborg, Jakob

AU - Payne, Mark Ronald

AU - Bartkova, Jirina

AU - Lindström, Mikael S

AU - Lukas, Jiri

AU - Andersen, Jens S.

AU - Bartek, Jiri

AU - Larsen, Dorthe Helena

PY - 2018/9/2

Y1 - 2018/9/2

N2 - Ionizing radiation (IR) causes DNA double-strand breaks (DSBs) and activates a versatile cellular response regulating DNA repair, cell-cycle progression, transcription, DNA replication and other processes. In recent years proteomics has emerged as a powerful tool deepening our understanding of this multifaceted response. In this study we use SILAC-based proteomics to specifically investigate dynamic changes in cytoplasmic protein abundance after ionizing radiation; we present in-depth bioinformatics analysis and show that levels of proteins involved in autophagy (cathepsins and other lysosomal proteins), proteasomal degradation (Ubiquitin-related proteins), energy metabolism (mitochondrial proteins) and particularly translation (ribosomal proteins and translation factors) are regulated after cellular exposure to ionizing radiation. Downregulation of no less than 68 ribosomal proteins shows rapid changes in the translation pattern after IR. Additionally, we provide evidence of compartmental cytosol-nuclear translocation of numerous DNA damage related proteins using protein correlation profiling. In conclusion, these results highlight unexpected cytoplasmic processes actively orchestrated after genotoxic insults and protein translocation from the cytoplasm to the nucleus as a fundamental regulatory mechanism employed to aid cell survival and preservation of genome integrity.

AB - Ionizing radiation (IR) causes DNA double-strand breaks (DSBs) and activates a versatile cellular response regulating DNA repair, cell-cycle progression, transcription, DNA replication and other processes. In recent years proteomics has emerged as a powerful tool deepening our understanding of this multifaceted response. In this study we use SILAC-based proteomics to specifically investigate dynamic changes in cytoplasmic protein abundance after ionizing radiation; we present in-depth bioinformatics analysis and show that levels of proteins involved in autophagy (cathepsins and other lysosomal proteins), proteasomal degradation (Ubiquitin-related proteins), energy metabolism (mitochondrial proteins) and particularly translation (ribosomal proteins and translation factors) are regulated after cellular exposure to ionizing radiation. Downregulation of no less than 68 ribosomal proteins shows rapid changes in the translation pattern after IR. Additionally, we provide evidence of compartmental cytosol-nuclear translocation of numerous DNA damage related proteins using protein correlation profiling. In conclusion, these results highlight unexpected cytoplasmic processes actively orchestrated after genotoxic insults and protein translocation from the cytoplasm to the nucleus as a fundamental regulatory mechanism employed to aid cell survival and preservation of genome integrity.

U2 - 10.1080/15384101.2018.1515552

DO - 10.1080/15384101.2018.1515552

M3 - Journal article

C2 - 30196736

SN - 1538-4101

VL - 17

SP - 2146

EP - 2163

JO - Cell Cycle

JF - Cell Cycle

IS - 17

ER -

DNA damage-induced dynamic changes in abundance and cytosol-nuclear translocation of proteins involved in translational processes, metabolism, and autophagy

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