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MYC Protein Interactome Profiling Reveals Functionally Distinct Regions that Cooperate to Drive Tumorigenesis.

Molecular cell | 2018

Transforming members of the MYC family (MYC, MYCL1, and MYCN) encode transcription factors containing six highly conserved regions, termed MYC homology boxes (MBs). By conducting proteomic profiling of the MB interactomes, we demonstrate that half of the MYC interactors require one or more MBs for binding. Comprehensive phenotypic analyses reveal that two MBs, MB0 and MBII, are universally required for transformation. MBII mediates interactions with acetyltransferase-containing complexes, enabling histone acetylation, and is essential for MYC-dependent tumor initiation. By contrast, MB0 mediates interactions with transcription elongation factors via direct binding to the general transcription factor TFIIF. MB0 is dispensable for tumor initiation but is a major accelerator of tumor growth. Notably, the full transforming activity of MYC can be restored by co-expression of the non-transforming MB0 and MBII deletion proteins, indicating that these two regions confer separate molecular functions, both of which are required for oncogenic MYC activity.

Pubmed ID: 30415952 RIS Download

Associated grants

  • Agency: CIHR, Canada
  • Agency: Wellcome Trust, United Kingdom

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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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eXpress (tool)

RRID:SCR_006873

THIS RESOURCE IS NO LONGER IN SERVICE. Documented January 29, 2018.
From website: "Note that the eXpress software is also no longer being developed. We recommend you use kallisto instead." Kallisto can be found at http://pachterlab.github.io/kallisto/.

Software for streaming quantification for high-throughput DNA/RNA sequencing.
Can be used in any application where abundances of target sequences need to be estimated from short reads sequenced from them.

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SAM format (tool)

RRID:SCR_012093

A generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.

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New England Biolabs (tool)

RRID:SCR_013517

An Antibody supplier

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STAR (tool)

RRID:SCR_004463

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Anti-alpha-Tubulin Mouse mAb (DM1A) (antibody)

RRID:AB_2617116

This monoclonal targets alpha-Tubulin

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V5 tag antibody [SV5-Pk1] (antibody)

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Ki67 Antibody (antibody)

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Monoclonal Mouse Anti Human Smooth Muscle Actin (antibody)

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p63 Protein (antibody)

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Anti-Myc Tag (antibody)

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TFIIF antibody - ChIP Grade (antibody)

RRID:AB_778325

This polyclonal targets Human TFIIF - ChIP Grade

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Acetyl-Histone H4 (Lys8) Antibody (antibody)

RRID:AB_2248400

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TFIIF antibody - ChIP Grade (antibody)

RRID:AB_2114552

This polyclonal targets Human TFIIF - ChIP Grade

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Pol II (F-12) (antibody)

RRID:AB_630203

This monoclonal targets Pol II (F-12)

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CDK9 (C12F7) (antibody)

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Histone H3 (acetyl K9 + K14 + K18 + K23 + K27) antibody - ChIP Grade (antibody)

RRID:AB_873860

This polyclonal targets Histone H3 (acetyl K9 + K14 + K18 + K23 + K27) antibody - ChIP Grade

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Anti-Histone H4 (acetyl K5 + K8 + K12 + K16) antibody (antibody)

RRID:AB_2732882

This monoclonal targets Anti-Histone H4 (acetyl K5 + K8 + K12 + K16)

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ProteoWizard (software resource)

RRID:SCR_012056

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BlobFinder (data processing software)

RRID:SCR_015788

Software that can perform calculations on cells from fluorescence microscopy images. BlobFinder can perform two types of analysis: an average count analysis to count the number of fluorescent signals and nuclei in an image, and a single cell analysis to simulate a cytoplasm and assign each signal to a particular cell.

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Cytoscape (software resource)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

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Enrichr (software resource)

RRID:SCR_001575

A web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.

View all literature mentions

STAR (software resource)

RRID:SCR_015899

Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.

View all literature mentions

phantompeakqualtools (software resource)

RRID:SCR_005331

Software package that computes quick but highly informative enrichment and quality measures for ChIP-seq/DNase-seq/FAIRE-seq/MNase-seq data. It can also be used to obtain robust estimates of the predominant fragment length or characteristic tag shift values in these assays.

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EBSeq (software resource)

RRID:SCR_003526

Software R package for RNA-Seq Differential Expression Analysis.

View all literature mentions

SAMTOOLS (software resource)

RRID:SCR_002105

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MACS (software resource)

RRID:SCR_013291

Software Python package for identifying transcript factor binding sites. Used to evaluate significance of enriched ChIP regions. Improves spatial resolution of binding sites through combining information of both sequencing tag position and orientation. Can be used for ChIP-Seq data alone, or with control sample with increase of specificity.

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STRING (data or information resource)

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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edgeR (software resource)

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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BlobFinder (data processing software)

RRID:SCR_015788

Software that can perform calculations on cells from fluorescence microscopy images. BlobFinder can perform two types of analysis: an average count analysis to count the number of fluorescent signals and nuclei in an image, and a single cell analysis to simulate a cytoplasm and assign each signal to a particular cell.

View all literature mentions

Enrichr (software resource)

RRID:SCR_001575

A web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.

View all literature mentions

phantompeakqualtools (software resource)

RRID:SCR_005331

Software package that computes quick but highly informative enrichment and quality measures for ChIP-seq/DNase-seq/FAIRE-seq/MNase-seq data. It can also be used to obtain robust estimates of the predominant fragment length or characteristic tag shift values in these assays.

View all literature mentions

EBSeq (software resource)

RRID:SCR_003526

Software R package for RNA-Seq Differential Expression Analysis.

View all literature mentions

ProteoWizard (software resource)

RRID:SCR_012056

Software that enables rapid tool creation by providing a robust, pluggable development framework that simplifies and unifies data file access, and performs standard proteomics and LCMS dataset computations.

View all literature mentions

STRING (data or information resource)

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)

View all literature mentions

SAMTOOLS (software resource)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

View all literature mentions

STAR (software resource)

RRID:SCR_015899

Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.

View all literature mentions

MACS (software resource)

RRID:SCR_013291

Software Python package for identifying transcript factor binding sites. Used to evaluate significance of enriched ChIP regions. Improves spatial resolution of binding sites through combining information of both sequencing tag position and orientation. Can be used for ChIP-Seq data alone, or with control sample with increase of specificity.

View all literature mentions

edgeR (software resource)

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.

View all literature mentions

Cytoscape (software resource)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

View all literature mentions