Limits...
The Role of Translational Regulation in Survival after Radiation Damage; an Opportunity for Proteomics Analysis.

Stickel S, Gomes N, Su TT - Proteomes (2014)

Bottom Line: Furthermore, changes in the post-translational modifications of proteins (phosphorylation, acetylation as well as degradation) are profoundly important for the cellular response to IR.These considerations make proteomics a highly suitable tool for mechanistic studies of the effect of IR.Strikingly such studies remain outnumbered by those utilizing proteomics for diagnostic purposes such as the identification of biomarkers for the outcome of radiation therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.

ABSTRACT

In this review, we will summarize the data from different model systems that illustrate the need for proteome-wide analyses of the biological consequences of ionizing radiation (IR). IR remains one of three main therapy choices for oncology, the others being surgery and chemotherapy. Understanding how cells and tissues respond to IR is essential for improving therapeutic regimes against cancer. Numerous studies demonstrating the changes in the transcriptome following exposure to IR, in diverse systems, can be found in the scientific literature. However, the limitation of our knowledge is illustrated by the fact that the number of transcripts that change after IR exposure is approximately an order of magnitude lower than the number of transcripts that re-localize to or from ribosomes under similar conditions. Furthermore, changes in the post-translational modifications of proteins (phosphorylation, acetylation as well as degradation) are profoundly important for the cellular response to IR. These considerations make proteomics a highly suitable tool for mechanistic studies of the effect of IR. Strikingly such studies remain outnumbered by those utilizing proteomics for diagnostic purposes such as the identification of biomarkers for the outcome of radiation therapy. Here we will discuss the role of the ribosome and translational regulation in the survival and preservation of cells and tissues after exposure to ionizing radiation. In doing so we hope to provide a strong incentive for the study of proteome-wide changes following IR exposure.

No MeSH data available.


Related in: MedlinePlus

DNA damage responses that would be amenable to proteomic analysis. Ionization Radiation (IR) causes DNA single and double strand breaks that result in three canonical responses: activation of cell cycle checkpoints, induction of DNA repair and cell death by apoptosis (blue arrows and boxes). In metazoa, dying cells exert non-autonomous effects (red) that include the radiation bystander effect, compensatory or apoptosis-induced cell proliferation, the Phoenix Rising effect and the Mahakali effect. All of these responses involve alterations in the proteomes through changes in transcription, translational regulation, post-translational modification and protein degradation. See text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4530795&req=5

Figure 1: DNA damage responses that would be amenable to proteomic analysis. Ionization Radiation (IR) causes DNA single and double strand breaks that result in three canonical responses: activation of cell cycle checkpoints, induction of DNA repair and cell death by apoptosis (blue arrows and boxes). In metazoa, dying cells exert non-autonomous effects (red) that include the radiation bystander effect, compensatory or apoptosis-induced cell proliferation, the Phoenix Rising effect and the Mahakali effect. All of these responses involve alterations in the proteomes through changes in transcription, translational regulation, post-translational modification and protein degradation. See text for details.

Mentions: Ionizing radiation (IR) collectively refers to radiation (X-rays and γ-rays) and high-energy particles (alpha and beta particles) with sufficient energy to break not only chemical bonds but also atoms into ions [1]. The most prominent consequences to IR-treated cells are DNA single and double-strand breaks (DSB) [2–4]. The preponderance of these breaks occur following DNA interaction with reactive oxygen species generated by the ionization of water, and to a lesser extent by the direct cleavage of phosphodiester bonds by IR [1]. If left unrepaired DSBs are highly lethal; therefore, cells employ a plethora of responses collectively known as DNA damage responses (DDR) to efficiently repair these DNA lesions. Canonical DDR encompasses the combination of several key cellular responses including cell cycle arrest by checkpoint activation, DNA repair and/or cell death (typically via apoptosis). DDR has been described in several excellent reviews (e.g., [2,5–7]), and will not be covered in detail here. However we will briefly discuss the secondary consequences of IR-induced cell death in the following paragraphs as this appears to be important for the survival of tissues and organisms (Figure 1).


The Role of Translational Regulation in Survival after Radiation Damage; an Opportunity for Proteomics Analysis.

Stickel S, Gomes N, Su TT - Proteomes (2014)

DNA damage responses that would be amenable to proteomic analysis. Ionization Radiation (IR) causes DNA single and double strand breaks that result in three canonical responses: activation of cell cycle checkpoints, induction of DNA repair and cell death by apoptosis (blue arrows and boxes). In metazoa, dying cells exert non-autonomous effects (red) that include the radiation bystander effect, compensatory or apoptosis-induced cell proliferation, the Phoenix Rising effect and the Mahakali effect. All of these responses involve alterations in the proteomes through changes in transcription, translational regulation, post-translational modification and protein degradation. See text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530795&req=5

Figure 1: DNA damage responses that would be amenable to proteomic analysis. Ionization Radiation (IR) causes DNA single and double strand breaks that result in three canonical responses: activation of cell cycle checkpoints, induction of DNA repair and cell death by apoptosis (blue arrows and boxes). In metazoa, dying cells exert non-autonomous effects (red) that include the radiation bystander effect, compensatory or apoptosis-induced cell proliferation, the Phoenix Rising effect and the Mahakali effect. All of these responses involve alterations in the proteomes through changes in transcription, translational regulation, post-translational modification and protein degradation. See text for details.
Mentions: Ionizing radiation (IR) collectively refers to radiation (X-rays and γ-rays) and high-energy particles (alpha and beta particles) with sufficient energy to break not only chemical bonds but also atoms into ions [1]. The most prominent consequences to IR-treated cells are DNA single and double-strand breaks (DSB) [2–4]. The preponderance of these breaks occur following DNA interaction with reactive oxygen species generated by the ionization of water, and to a lesser extent by the direct cleavage of phosphodiester bonds by IR [1]. If left unrepaired DSBs are highly lethal; therefore, cells employ a plethora of responses collectively known as DNA damage responses (DDR) to efficiently repair these DNA lesions. Canonical DDR encompasses the combination of several key cellular responses including cell cycle arrest by checkpoint activation, DNA repair and/or cell death (typically via apoptosis). DDR has been described in several excellent reviews (e.g., [2,5–7]), and will not be covered in detail here. However we will briefly discuss the secondary consequences of IR-induced cell death in the following paragraphs as this appears to be important for the survival of tissues and organisms (Figure 1).

Bottom Line: Furthermore, changes in the post-translational modifications of proteins (phosphorylation, acetylation as well as degradation) are profoundly important for the cellular response to IR.These considerations make proteomics a highly suitable tool for mechanistic studies of the effect of IR.Strikingly such studies remain outnumbered by those utilizing proteomics for diagnostic purposes such as the identification of biomarkers for the outcome of radiation therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.

ABSTRACT

In this review, we will summarize the data from different model systems that illustrate the need for proteome-wide analyses of the biological consequences of ionizing radiation (IR). IR remains one of three main therapy choices for oncology, the others being surgery and chemotherapy. Understanding how cells and tissues respond to IR is essential for improving therapeutic regimes against cancer. Numerous studies demonstrating the changes in the transcriptome following exposure to IR, in diverse systems, can be found in the scientific literature. However, the limitation of our knowledge is illustrated by the fact that the number of transcripts that change after IR exposure is approximately an order of magnitude lower than the number of transcripts that re-localize to or from ribosomes under similar conditions. Furthermore, changes in the post-translational modifications of proteins (phosphorylation, acetylation as well as degradation) are profoundly important for the cellular response to IR. These considerations make proteomics a highly suitable tool for mechanistic studies of the effect of IR. Strikingly such studies remain outnumbered by those utilizing proteomics for diagnostic purposes such as the identification of biomarkers for the outcome of radiation therapy. Here we will discuss the role of the ribosome and translational regulation in the survival and preservation of cells and tissues after exposure to ionizing radiation. In doing so we hope to provide a strong incentive for the study of proteome-wide changes following IR exposure.

No MeSH data available.


Related in: MedlinePlus