Limits...
Dissecting apoptosis the omics way.

Van Damme P - Elife (2013)

Bottom Line: A combined analysis of transcription, translation and protein degradation reveals the global effects of an anticancer drug on tumour cells.

View Article: PubMed Central - PubMed

Affiliation: Petra Van Damme is at the Department of Medical Protein Research, VIB, and Department of Biochemistry, Ghent University, Ghent, Belgium petra.vandamme@vib-ugent.be.

ABSTRACT
A combined analysis of transcription, translation and protein degradation reveals the global effects of an anticancer drug on tumour cells.

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Related in: MedlinePlus

A schematic to show how translation efficiency can be assessed by means of ribosome profiling.The production of a protein from a gene involves transcription, which can be measured in terms of mRNA sequence reads (red), and translation, which can be measured in terms of ribosome footprints (blue). (A) Relative to a baseline condition (top), bortezomib increases both the transcription and the translation of certain genes, as can be seen from the mRNA levels and the ribosome footprints (bottom). (B) Bortezomib can also decrease both transcription and translation. For other genes, bortezomib had differing effects on these two processes: an increase in protein levels relative to baseline, despite a reduction in mRNA, indicates that the efficiency of translation is increased (C); and a reduction in protein levels relative to baseline, despite no change in mRNA, indicates that the efficiency of translation is reduced (D).
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fig1: A schematic to show how translation efficiency can be assessed by means of ribosome profiling.The production of a protein from a gene involves transcription, which can be measured in terms of mRNA sequence reads (red), and translation, which can be measured in terms of ribosome footprints (blue). (A) Relative to a baseline condition (top), bortezomib increases both the transcription and the translation of certain genes, as can be seen from the mRNA levels and the ribosome footprints (bottom). (B) Bortezomib can also decrease both transcription and translation. For other genes, bortezomib had differing effects on these two processes: an increase in protein levels relative to baseline, despite a reduction in mRNA, indicates that the efficiency of translation is increased (C); and a reduction in protein levels relative to baseline, despite no change in mRNA, indicates that the efficiency of translation is reduced (D).

Mentions: By comparing the number of ribosome footprints with the number of mRNA sequencing reads, it was possible to deduce the efficiency of translation within the tumour cells (Figure 1). In line with previous reports, they found that bortezomib—which inhibits a complex called the proteasome—caused misfolded proteins to accumulate inside cells. As a result, the endoplasmic reticulum (which is involved in protein trafficking) became overwhelmed, triggering the unfolded protein response (Obeng et al., 2006). This leads to a series of cellular processes to counteract the accumulation of misfolded proteins, including increased protein folding, inhibition of translation, and, as a last resort, the induction of apoptosis. Witta et al. showed that bortezomib increased both transcription and translation of a number of genes involved in the folding or degradation of proteins, and downregulated the expression of genes involved in cellular proliferation.Figure 1.A schematic to show how translation efficiency can be assessed by means of ribosome profiling.


Dissecting apoptosis the omics way.

Van Damme P - Elife (2013)

A schematic to show how translation efficiency can be assessed by means of ribosome profiling.The production of a protein from a gene involves transcription, which can be measured in terms of mRNA sequence reads (red), and translation, which can be measured in terms of ribosome footprints (blue). (A) Relative to a baseline condition (top), bortezomib increases both the transcription and the translation of certain genes, as can be seen from the mRNA levels and the ribosome footprints (bottom). (B) Bortezomib can also decrease both transcription and translation. For other genes, bortezomib had differing effects on these two processes: an increase in protein levels relative to baseline, despite a reduction in mRNA, indicates that the efficiency of translation is increased (C); and a reduction in protein levels relative to baseline, despite no change in mRNA, indicates that the efficiency of translation is reduced (D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824024&req=5

fig1: A schematic to show how translation efficiency can be assessed by means of ribosome profiling.The production of a protein from a gene involves transcription, which can be measured in terms of mRNA sequence reads (red), and translation, which can be measured in terms of ribosome footprints (blue). (A) Relative to a baseline condition (top), bortezomib increases both the transcription and the translation of certain genes, as can be seen from the mRNA levels and the ribosome footprints (bottom). (B) Bortezomib can also decrease both transcription and translation. For other genes, bortezomib had differing effects on these two processes: an increase in protein levels relative to baseline, despite a reduction in mRNA, indicates that the efficiency of translation is increased (C); and a reduction in protein levels relative to baseline, despite no change in mRNA, indicates that the efficiency of translation is reduced (D).
Mentions: By comparing the number of ribosome footprints with the number of mRNA sequencing reads, it was possible to deduce the efficiency of translation within the tumour cells (Figure 1). In line with previous reports, they found that bortezomib—which inhibits a complex called the proteasome—caused misfolded proteins to accumulate inside cells. As a result, the endoplasmic reticulum (which is involved in protein trafficking) became overwhelmed, triggering the unfolded protein response (Obeng et al., 2006). This leads to a series of cellular processes to counteract the accumulation of misfolded proteins, including increased protein folding, inhibition of translation, and, as a last resort, the induction of apoptosis. Witta et al. showed that bortezomib increased both transcription and translation of a number of genes involved in the folding or degradation of proteins, and downregulated the expression of genes involved in cellular proliferation.Figure 1.A schematic to show how translation efficiency can be assessed by means of ribosome profiling.

Bottom Line: A combined analysis of transcription, translation and protein degradation reveals the global effects of an anticancer drug on tumour cells.

View Article: PubMed Central - PubMed

Affiliation: Petra Van Damme is at the Department of Medical Protein Research, VIB, and Department of Biochemistry, Ghent University, Ghent, Belgium petra.vandamme@vib-ugent.be.

ABSTRACT
A combined analysis of transcription, translation and protein degradation reveals the global effects of an anticancer drug on tumour cells.

Show MeSH
Related in: MedlinePlus