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Widespread Post-transcriptional Attenuation of Genomic Copy-Number Variation in Cancer.

Cell systems | 2017

Copy-number variations (CNVs) are ubiquitous in cancer and often act as driver events, but the effects of CNVs on the proteome of tumors are poorly understood. Here, we analyze recently published genomics, transcriptomics, and proteomics datasets made available by CPTAC and TCGA consortia on 282 breast, ovarian, and colorectal tumor samples to investigate the impact of CNVs in the proteomes of these cells. We found that CNVs are buffered by post-transcriptional regulation in 23%-33% of proteins that are significantly enriched in protein complex members. Our analyses show that complex subunits are highly co-regulated, and some act as rate-limiting steps of complex assembly, as their depletion induces decreased abundance of other complex members. We identified 48 such rate-limiting interactions and experimentally confirmed our predictions on the interactions of AP3B1 with AP3M1 and GTF2E2 with GTF2E1. This study highlights the importance of post-transcriptional mechanisms in cancer that allow cells to cope with their altered genomes.

Pubmed ID: 29032074 RIS Download

Associated grants

None

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This is a list of tools and resources that we have found mentioned in this publication.


Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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Bio-Rad Laboratories (tool)

RRID:SCR_008426

Commercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.

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GraphPad (tool)

RRID:SCR_000306

A commercial graphing software company that offers scientific software for statistical analyses, curve fitting and data analysis. It offers four programs: Prism, InStat, StatMate and QuickCalcs.

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scikit-learn (tool)

RRID:SCR_002577

scikit-learn: machine learning in Python

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edgeR (tool)

RRID:SCR_012802

Bioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.

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STRING (tool)

RRID:SCR_005223

Database of known and predicted protein interactions. The interactions include direct (physical) and indirect (functional) associations and are derived from four sources: Genomic Context, High-throughput experiments, (Conserved) Coexpression, and previous knowledge. STRING quantitatively integrates interaction data from these sources for a large number of organisms, and transfers information between these organisms where applicable. The database currently covers 5''214''234 proteins from 1133 organisms. (2013)

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MatPlotLib (tool)

RRID:SCR_008624

Python 2D plotting library which produces publication quality figures in variety of hardcopy formats and interactive environments across platforms. Used in python scripts, web application servers, and six graphical user interface toolkits. Used to generate plots, histograms, power spectra, bar charts, error charts, scatter plots.

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LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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RRID:AB_2099233

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GAPDH (D16H11) XP Rabbit mAb (antibody)

RRID:AB_10622025

This monoclonal targets GAPDH

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Anti-TFIIE beta antibody [EPR14929] (antibody)

RRID:AB_2715540

This monoclonal targets TFIIE beta

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Anti-TFIIE alpha antibody [EPR8377(2)] (antibody)

RRID:AB_2715539

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AP3B1 purified MaxPab mouse polyclonal antibody (B01P) (antibody)

RRID:AB_10714215

This polyclonal targets AP3B1 purified MaxPab mouse polyclonal antibody (B01P)

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HEK293 (cell line)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

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HCT 116 (cell line)

RRID:CVCL_0291

Cell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)

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HEK293 (cell line)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HCT 116 (cell line)

RRID:CVCL_0291

Cell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)

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Anti-rabbit IgG, HRP-linked Antibody (antibody)

RRID:AB_2099233

This polyclonal secondary targets IgG

View all literature mentions

GAPDH (D16H11) XP Rabbit mAb (antibody)

RRID:AB_10622025

This monoclonal targets GAPDH

View all literature mentions

Anti-TFIIE beta antibody [EPR14929] (antibody)

RRID:AB_2715540

This monoclonal targets TFIIE beta

View all literature mentions

Anti-TFIIE alpha antibody [EPR8377(2)] (antibody)

RRID:AB_2715539

This monoclonal targets TFIIE alpha

View all literature mentions

AP3B1 purified MaxPab mouse polyclonal antibody (B01P) (antibody)

RRID:AB_10714215

This polyclonal targets AP3B1 purified MaxPab mouse polyclonal antibody (B01P)

View all literature mentions

HEK293 (cell line)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HCT 116 (cell line)

RRID:CVCL_0291

Cell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Anti-rabbit IgG, HRP-linked Antibody (antibody)

RRID:AB_2099233

This polyclonal secondary targets IgG

View all literature mentions

GAPDH (D16H11) XP Rabbit mAb (antibody)

RRID:AB_10622025

This monoclonal targets GAPDH

View all literature mentions

Anti-TFIIE beta antibody [EPR14929] (antibody)

RRID:AB_2715540

This monoclonal targets TFIIE beta

View all literature mentions

Anti-TFIIE alpha antibody [EPR8377(2)] (antibody)

RRID:AB_2715539

This monoclonal targets TFIIE alpha

View all literature mentions

AP3B1 purified MaxPab mouse polyclonal antibody (B01P) (antibody)

RRID:AB_10714215

This polyclonal targets AP3B1 purified MaxPab mouse polyclonal antibody (B01P)

View all literature mentions