PXD018223-2

PXD018223 is an original dataset announced via ProteomeXchange.

Title	Quantitative Proteomics of Mouse Liver (FTO-KO,WT) in response to DEN injection
Description	Single nucleotide polymorphisms in the FTO gene encoding a m6A demthylase are associated with obesity and cancer development. However, the functional role of FTO in the developemnt of progression of hepatocellular carcinoma (HCC) as a proteotypic obesity-associated cancer remains unclear. Here, we have generated mice with hepatic FTO deficiency (FTOL-KO) and subjected them to DEN induced HCC-development. FTOL-KO mice exhibit increased HCC burden. While control mice exhibit a dynamic regulation of FTO upon induction of liver damage, this response is abrogated in mice lacking FTO. Proteomic analyses revealed that liver damage-induced increases in FTO expression promotes m6A-demethylation of CUL4A reducing its protein expression. Functionally, knockdown of CUL4A restores the increased hepatocyte proliferation observed upon loss of FTO. Collectively, our study reveals a protective role for FTO-dependent dynamic m6A mRNA demethylation of CUL4A in the initiation of HCC development.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:14:32.217.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hendrik Nolte
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-26 22:59:27	ID requested
1	2020-11-02 23:24:33	announced
⏵ 2	2024-10-22 05:14:33	announced	2024-10-22: Updated project metadata.

10.1016/j.molmet.2020.101085;

Mittenb, ü, hler MJ, Saedler K, Nolte H, Kern L, Zhou J, Qian SB, Meder L, Ullrich RT, Br, ü, ning JC, Wunderlich FT, vivo. Mol Metab, 42():101085(2020) [pubmed]

submitter keyword: FTO, DEN, CUL4A, liver

Thomas Langer
contact affiliation	Max-Planck-Institute for Biology of Ageing Department of Mitochondrial Proteostasis Joseph-Stelzmann-Str. 9b 50931 Cologne
contact email	tlanger@age.mpg.de
lab head
Hendrik Nolte
contact affiliation	Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany
contact email	h.nolte@age.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/11/PXD018223

PRIDE project URI

• PRIDE
  1. PXD018223
     1. Label: PRIDE project
     2. Name: Quantitative Proteomics of Mouse Liver (FTO-KO,WT) in response to DEN injection