PXD010095 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | C/EBPβ-LIP regulates the let-7/Lin28b circuit to induce cancer-type metabolic reprogramming |
Description | The RNA binding protein Lin28b is highly expressed during embryogenesis but its expression declines in adult tissues, and aberrant expression of Lin28b is associated with tumour development and maintenance. Lin28b regulates the translation of several glycolytic and mitochondrial enzymes in order to enhance cellular metabolism and energy production. Lin28b is repressed by let-7 family microRNAs in a reciprocal negative regulatory circuitry where Lin28b supresses maturation of let-7. This circuitry obtains input from master regulators such as MYC that transcriptionally upregulates Lin28b, which is required for let-7 suppression and proliferation. Not much is known of how this circuitry is regulated through transcription of the let-7 microRNAs. Here we show that the transcription factor C/EBPβ-LIP induces aerobic glycolysis and mitochondrial respiration reminiscent to cancer cell metabolism. By integrating transcriptome, proteome and metabolic flux analysis we reveal that this LIP-induced metabolic reprogramming is dependent on Lin28b and that LIP enhances Lin28b expression through transcriptional repression of the let-7 microRNA family. Transgenic mice overexpressing LIP have reduced levels of let-7 in bone marrow, skin and spleen, which is associated with induction of Lin28b and hyperplasia. This study establishes LIP as a regulator of the let-7/Lin28b regulatory circuitry and we hypothesize that the LIP-controlled let-7/Lin28b regulation is involved in the de-regulation of tissue homeostasis and tumourigenesis. |
HostingRepository | PRIDE |
AnnounceDate | 2019-11-12 |
AnnouncementXML | Submission_2019-11-12_11:38:38.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Guido Mastrobuoni |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-06-11 08:42:12 | ID requested | |
⏵ 1 | 2019-11-12 11:38:40 | announced | |
Publication List
Ackermann T, Hartleben G, M, ü, ller C, Mastrobuoni G, Groth M, Sterken BA, Zaini MA, Youssef SA, Zuidhof HR, Krauss SR, Kortman G, de Haan G, de Bruin A, Wang ZQ, Platzer M, Kempa S, Calkhoven CF, /LIN28B circuit in mice. Commun Biol, 2():208(2019) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: shotgun proteomics, Q Exactive HF |
Contact List
Stefan Kempa |
contact affiliation | Quantitative Proteomics and Metabolomics Berlin Institute for Medical System Biology @ Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association |
contact email | stefan.kempa@mdc-berlin.de |
lab head | |
Guido Mastrobuoni |
contact affiliation | Berlin Institute for Medical Systems Biology at the Max Delbrueck Centrum for Molecular Medicine |
contact email | guido.mastrobuoni@mdc-berlin.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD010095
- Label: PRIDE project
- Name: C/EBPβ-LIP regulates the let-7/Lin28b circuit to induce cancer-type metabolic reprogramming