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

Eukaryotic translation initiation and elongation. Protein factors required are shown in the box next to each step. Of these, the ones known to be regulated or modified following exposure to ionizing radiation are in red font. The diamond represents the tri-methyl-G cap on the mRNA. Internal ribosome entry site (IRES) represents the internal ribosome entry site used in cap-independent initiation. The mRNA (black line) is depicted as linear for the sake of clarity, but would in reality be circularized as the 5' and the 3' ends interact via proteins bound. The ovals represent the ribosome and the dashed line represents the nascent polypeptide chain. ITAFs = IRES transacting factors. PABP = Poly A binding protein. The termination step is not shown. See text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Eukaryotic translation initiation and elongation. Protein factors required are shown in the box next to each step. Of these, the ones known to be regulated or modified following exposure to ionizing radiation are in red font. The diamond represents the tri-methyl-G cap on the mRNA. Internal ribosome entry site (IRES) represents the internal ribosome entry site used in cap-independent initiation. The mRNA (black line) is depicted as linear for the sake of clarity, but would in reality be circularized as the 5' and the 3' ends interact via proteins bound. The ovals represent the ribosome and the dashed line represents the nascent polypeptide chain. ITAFs = IRES transacting factors. PABP = Poly A binding protein. The termination step is not shown. See text for details.

Mentions: Translation occurs in three distinct stages: initiation, elongation, and termination (Figure 2). Under normal conditions, initiation is rate-limiting and involves the assembly of the pre-initiation complex (PIC) and the mRNP complex [32]. The PIC is composed of a sub-complex of Met-tRNAi-eIF2-GDP, initiation factors eIF1, eIF1A, eIF 3, and eIF 5, and the small 40S ribosomal subunit. Generally, de novo protein synthesis is “cap-dependent”, requiring a 5' mRNA tri-methyl-guanine cap used to assemble the mRNP complex that is composed of circularized mRNA, initiation factors eIF4A, eIF4B, eIF4E, and eIF4G, in addition to the poly A-binding protein (PABP) [33–37]. The PIC and the mRNP associate to form the 43S-mRNA complex, which scans for the start (AUG) codon. Once the start codon is reached, the 60S ribosomal subunit joins to form the 80S ribosome complex and initiate elongation.


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

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

Eukaryotic translation initiation and elongation. Protein factors required are shown in the box next to each step. Of these, the ones known to be regulated or modified following exposure to ionizing radiation are in red font. The diamond represents the tri-methyl-G cap on the mRNA. Internal ribosome entry site (IRES) represents the internal ribosome entry site used in cap-independent initiation. The mRNA (black line) is depicted as linear for the sake of clarity, but would in reality be circularized as the 5' and the 3' ends interact via proteins bound. The ovals represent the ribosome and the dashed line represents the nascent polypeptide chain. ITAFs = IRES transacting factors. PABP = Poly A binding protein. The termination step is not shown. See text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Eukaryotic translation initiation and elongation. Protein factors required are shown in the box next to each step. Of these, the ones known to be regulated or modified following exposure to ionizing radiation are in red font. The diamond represents the tri-methyl-G cap on the mRNA. Internal ribosome entry site (IRES) represents the internal ribosome entry site used in cap-independent initiation. The mRNA (black line) is depicted as linear for the sake of clarity, but would in reality be circularized as the 5' and the 3' ends interact via proteins bound. The ovals represent the ribosome and the dashed line represents the nascent polypeptide chain. ITAFs = IRES transacting factors. PABP = Poly A binding protein. The termination step is not shown. See text for details.
Mentions: Translation occurs in three distinct stages: initiation, elongation, and termination (Figure 2). Under normal conditions, initiation is rate-limiting and involves the assembly of the pre-initiation complex (PIC) and the mRNP complex [32]. The PIC is composed of a sub-complex of Met-tRNAi-eIF2-GDP, initiation factors eIF1, eIF1A, eIF 3, and eIF 5, and the small 40S ribosomal subunit. Generally, de novo protein synthesis is “cap-dependent”, requiring a 5' mRNA tri-methyl-guanine cap used to assemble the mRNP complex that is composed of circularized mRNA, initiation factors eIF4A, eIF4B, eIF4E, and eIF4G, in addition to the poly A-binding protein (PABP) [33–37]. The PIC and the mRNP associate to form the 43S-mRNA complex, which scans for the start (AUG) codon. Once the start codon is reached, the 60S ribosomal subunit joins to form the 80S ribosome complex and initiate elongation.

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