PXD031088

PXD031088 is an original dataset announced via ProteomeXchange.

Title	Fatty acid transport protein 2 interacts with ceramide synthase 2 to regulate ceramide synthesis
Description	Dihydroceramide is generated via the action of (dihydro)ceramide synthases (CerSs), which use two substrates, namely sphinganine and fatty acyl CoAs. Sphinganine is generated via the sequential activity of two integral membrane proteins located in the endoplasmic reticulum. Less is known about the source of supply of the fatty acyl CoAs, although a number of cytosolic proteins in the pathways of acyl CoA generation have been shown to modulate ceramide synthesis via direct or indirect interaction with the CerSs. We now demonstrate, by proteomic analysis of immunoprecipitated proteins, that fatty acid transporter protein 2 (FATP2) (also known as very long-chain acyl-CoA synthetase) directly interacts with CerS2 in mouse liver. Studies in cultured cells demonstrated that other members of the FATP family can also interact with CerS2, with the interaction dependent on both proteins being catalytically active. Transfection of cells with FATP1, FATP2 or FATP4 increased ceramide levels although only FATP2 and 4 increased dihydroceramide levels, consistent with their known intracellular locations. Finally, lipofermata, an FATP2 inhibitor which is believed to directly impact tumor cell growth via modulation of FATP2, decreased de novo dihydroceramide synthesis, suggesting that some of the proposed therapeutic effects of lipofermata may actually be mediated via (dihydro)ceramide rather than directly via acyl CoA generation
HostingRepository	PRIDE
AnnounceDate	2022-05-25
AnnouncementXML	Submission_2022-05-25_09:31:00.075.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Meital Kupervaser
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-19 09:24:21	ID requested
⏵ 1	2022-05-25 09:31:01	announced

Kim JL, Mestre B, Malitsky S, Itkin M, Kupervaser M, Futerman AH, Fatty acid transport protein 2 interacts with ceramide synthase 2 to promote ceramide synthesis. J Biol Chem, 298(4):101735(2022) [pubmed]

submitter keyword: Ceramide, ceramide synthase, dihydroceramide, fatty acid transport protein, sphingolipids

Anthony H. Futerman
contact affiliation	Department Biomolecular Sciences and the Joseph Meyerhoff Professor of Biochemistry at the Weizmann Institute of Science, Rehovot 76100, Israel
contact email	tony.futerman@weizmann.ac.il
lab head
Meital Kupervaser
contact affiliation	Weizmann Institute of Science
contact email	meital.kupervaser@weizmann.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031088
     1. Label: PRIDE project
     2. Name: Fatty acid transport protein 2 interacts with ceramide synthase 2 to regulate ceramide synthesis