PXD023932

PXD023932 is an original dataset announced via ProteomeXchange.

Title	ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth
Description	A subset of Ras proteins, including N-Ras, depend on a palmitoylation/depalmitoylation cycle to regulate their subcellular trafficking and oncogenicity. General lipase inhibitors such as Palmostatin M block N-Ras depalmitoylation, but lack specificity and target several enzymes displaying depalmitoylase activity. Here, we describe ABD957, a potent and selective covalent inhibitor of the ABHD17 family of depalmitoylases, and show that this compound impairs N-Ras depalmitoylation in human acute myeloid leukemia (AML) cells. ABD957 produced partial effects on N-Ras palmitoylation compared to Palmostatin M, but was much more selective across the proteome, reflecting a plasma membrane-delineated action on dynamically palmitoylated proteins. Finally, ABD957 impaired N-Ras signaling and the growth of NRAS-mutant AML cells in a manner that synergizes with MEK inhibition. Our findings uncover a surprisingly restricted role for ABHD17 enzymes as regulators of the N-Ras palmitoylation cycle and suggest that ABHD17 inhibitors may have value as targeted therapies for NRAS-mutant cancers.
HostingRepository	PRIDE
AnnounceDate	2021-04-28
AnnouncementXML	Submission_2021-05-03_21:56:51.915.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jarrett Remsberg
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-02 01:42:31	ID requested
1	2021-04-27 22:17:50	announced
⏵ 2	2021-05-03 21:56:52	announced	2021-05-04: Updated publication reference for PubMed record(s): 33927411.

Remsberg JR, Suciu RM, Zambetti NA, Hanigan TW, Firestone AJ, Inguva A, Long A, Ngo N, Lum KM, Henry CL, Richardson SK, Predovic M, Huang B, Dix MM, Howell AR, Niphakis MJ, Shannon K, Cravatt BF, ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth. Nat Chem Biol, 17(8):856-864(2021) [pubmed]

submitter keyword: N-Ras, palmitoylation, ABHD17, human acute myeloid leukemia

Benjamin F. Cravatt
contact affiliation	Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA
contact email	cravatt@scripps.edu
lab head
Jarrett Remsberg
contact affiliation	Scripps Research Institute
contact email	remsberg@scripps.edu
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/2021/04/PXD023932

PRIDE project URI

• PRIDE
  1. PXD023932
     1. Label: PRIDE project
     2. Name: ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth