PXD020015-1

PXD020015 is an original dataset announced via ProteomeXchange.

Title	S-Adenosylmethionine Depletion Activates La Ribonucleoprotein Domain Family Member 1 to Induce Protein Translation
Description	S-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.
HostingRepository	PanoramaPublic
AnnounceDate	2020-06-26
AnnouncementXML	Submission_2020-06-26_05:56:17.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	Aaron Robinson
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090; scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Phospho; Oxidation; Carbamidomethyl
Instrument	Orbitrap Fusion Lumos; TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-25 05:42:13	ID requested
⏵ 1	2020-06-26 05:56:17	announced

Dataset with its publication pending

submitter keyword: NASH, liver, phospho, DIA, DDA, CDK2, Nonalcoholic Steatohepatitis, Hepatocellular carcinoma

Jennifer Van Eyk
contact affiliation	Cedars Sinai Medical Center
contact email	Jennifer.VanEyk@cshs.org
lab head
Aaron Robinson
contact affiliation	Cedars Sinai Medical Center
contact email	aaron.robinson@cshs.org
dataset submitter

Panorama Public dataset URI