Summary of Study ST001429
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000981. The data can be accessed directly via it's Project DOI: 10.21228/M8WD7R This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST001429 |
| Study Title | MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with Host Cell Factor-1 |
| Study Summary | MYC is an oncoprotein transcription factor that is overexpressed in the majority cancers. Although MYC itself is considered undruggable, it may be possible to inhibit MYC by targeting the co-factors it uses to drive oncogenic gene expression patterns. Here, we use loss- and gain- of function approaches to interrogate how one MYC co-factor—Host Cell Factor (HCF)-1—contributes to MYC activity in a Burkitt lymphoma setting. We identify high-confidence direct targets of the MYC–HCF-1 interaction that are regulated through a recruitment-independent mechanism, including genes that control mitochondrial function and rate-limiting steps for ribosome biogenesis and translation. We describe how these gene expression events impact cell growth and metabolism, and demonstrate that the MYC–HCF-1 interaction is essential for tumor maintenance in vivo. This work highlights the MYC–HCF-1 interaction as a focal point for development of novel anti-cancer therapies. |
| Institute | Vanderbilt University |
| Last Name | Codreanu |
| First Name | Simona |
| Address | 1234 Stevenson Center Lane |
| simona.codreanu@vanderbilt.edu | |
| Phone | 6158758422 |
| Submit Date | 2020-07-15 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2021-01-19 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO001498 |
| Collection Summary: | To understand the cellular consequences of modulating the MYC–HCF-1 interaction, we engineered a system that allows us to express the 4A or VP16 HBM mutant MYC proteins as the sole form of MYC in a cell. We chose Ramos cells, a Burkitt lymphoma (BL)-derived line in which a t(8;14) translocation places one c-MYC allele under regulatory control of the immunoglobulin heavy chain enhancer. The untranslocated c-MYC allele is not expressed in these cells. Because sequences encoding the MYC HBM are contained within exon 3, we used CRISPR/Cas9-triggered homologous recombination of the translocated MYC allele to integrate an exon 3 switchable cassette for wild-type (WT) MYC, 4A, or VP16 HBM mutants, and confirmed appropriate integration by Southern blotting. Thus, we successfully generated a system for inducible, selective, and bidirectional modulation of the MYC−HCF-1 interaction in the context of an archetypal MYC-driven cancer cell line. |
| Sample Type: | Lymphoma cells |
| Storage Conditions: | -80℃ |
