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PXD020015-1

PXD020015 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleS-Adenosylmethionine Depletion Activates La Ribonucleoprotein Domain Family Member 1 to Induce Protein Translation
DescriptionS-adenosylmethionine (SAMe) is the principal methyl donor synthesized by methionine adenosyltransferase 1A (MAT1A)-encoded enzyme in the liver. Mice lacking Mat1a have hepatic SAMe depletion, spontaneous development of non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). To understand how SAMe depletion drives liver pathologies we performed phospho-proteomics in Mat1a knockout (KO) mice livers and the most striking change was hyperphosphorylation of La-Related Protein 1 (LARP1), which in the unphosphorylated form negatively regulates translation of 5'-terminal oligopyrimidine (TOP)-containing mRNAs. Consistently, multiple TOP proteins are induced in the KO livers. We identified LARP1-T449 as a novel, SAMe-sensitive phospho-site of cyclin-dependent kinase 2. LARP1-T449 phosphorylation induced global translation, cell growth, migration, invasion, and expression of oncogenic TOP-ribosomal proteins in HCC cells. LARP1 expression is increased in human NASH and HCC. Our results reveal a novel SAMe-sensitive mechanism of LARP1 phosphorylation that may be involved in the progression of NASH to HCC.  
HostingRepositoryPanoramaPublic
AnnounceDate2020-06-26
AnnouncementXMLSubmission_2020-06-26_05:56:17.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportsupported by repository but incomplete data and/or metadata
PrimarySubmitterAaron Robinson
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090; scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListPhospho; Oxidation; Carbamidomethyl
InstrumentOrbitrap Fusion Lumos; TripleTOF 6600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-06-25 05:42:13ID requested
12020-06-26 05:56:17announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: NASH, liver, phospho, DIA, DDA, CDK2, Nonalcoholic Steatohepatitis, Hepatocellular carcinoma
Contact List
Jennifer Van Eyk
contact affiliationCedars Sinai Medical Center
contact emailJennifer.VanEyk@cshs.org
lab head
Aaron Robinson
contact affiliationCedars Sinai Medical Center
contact emailaaron.robinson@cshs.org
dataset submitter
Full Dataset Link List
Panorama Public dataset URI