Summary of Study ST001986
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 PR001262. The data can be accessed directly via it's Project DOI: 10.21228/M8KM58 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 | ST001986 |
| Study Title | Fbxo7 promotes Cdk6 activity to inhibit PFKP and glycolysis in T cells |
| Study Summary | Deregulated Fbxo7 expression is associated with many pathologies, including anaemia, male sterility, cancer, and Parkinson’s disease, demonstrating its critical role in a variety of cell types. Although Fbxo7 is an F-box protein that recruits substrates for SCF-type E3 ubiquitin ligases, it also promotes the formation of cyclin D/Cdk6/p27 complexes in an E3-ligase independent fashion. We discovered PFKP, the major gatekeeper of glycolysis, in a screen for Fbxo7 substrates. PFKP has been previously shown to be a critical substrate of Cdk6 for the viability of T-ALL cells experiencing high levels of reactive oxygen species. We investigated the molecular relationships between Fbxo7, Cdk6 and PFKP, and the functional effect Fbxo7 has on T cell metabolism, viability, and activation. Fbxo7 promotes Cdk6-independent ubiquitination and Cdk6-dependent phosphorylation of PFKP. Importantly Fbxo7-deficient cells have reduced Cdk6 activity, and haematopoietic and lymphocytic cell lines show a significant dependency on Fbxo7. CD4+ T cells with reduced Fbxo7 have increased glycolysis, and lower cell viability and activation levels. Metabolomic studies of activated CD4+ T cells confirm increased glycolytic flux in Fbxo7-deficient cells, as well as altered nucleotide biosynthesis and arginine metabolism. We show Fbxo7 expression is glucose-responsive, and we propose Fbxo7 inhibits PFKP and glycolysis via its activation of Cdk6. |
| Institute | University of Cambridge |
| Department | Department of Pathology |
| Laboratory | Laman Lab |
| Last Name | Laman |
| First Name | Heike |
| Address | Tennis Court Road, Cambridge CB2 1QP, UK. |
| hl316@cam.ac.uk | |
| Phone | +44 (0)1223 333722 |
| Submit Date | 2021-10-29 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-11-16 |
| Release Version | 1 |
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Factors:
Subject type: Cultured cells; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Sample groups | Treatment |
|---|---|---|---|
| SA185837 | RH2-09 | Mutant | unlabelled |
| SA185838 | RH2-10 | Mutant | unlabelled |
| SA185839 | RH2-12 | Mutant | unlabelled |
| SA185840 | RH2-08 | Mutant | unlabelled |
| SA185841 | RH2-11 | Mutant | unlabelled |
| SA185842 | RH2-07 | Mutant | unlabelled |
| SA185843 | RH2-03 | Wild type | unlabelled |
| SA185844 | RH2-02 | Wild type | unlabelled |
| SA185845 | RH2-04 | Wild type | unlabelled |
| SA185846 | RH2-05 | Wild type | unlabelled |
| SA185847 | RH2-06 | Wild type | unlabelled |
| SA185848 | RH2-01 | Wild type | unlabelled |
| Showing results 1 to 12 of 12 |
