PXD024603-1

PXD024603 is an original dataset announced via ProteomeXchange.

Title	ArfGAP1 inhibits mTORC1 lysosomal localization and activation
Description	The mammalian target of rapamycin complex 1 (mTORC1) integrates nutrients, growth factors, stress, and energy status to regulate cell growth and metabolism. Amino acids promote mTORC1 lysosomal localization and subsequent activation. However, the subcellular location or interacting proteins of mTORC1 under amino acid deficient conditions is not completely understood. Here, we identify ADP-ribosylation factor GTPase-activating protein 1 (ArfGAP1) as a crucial regulator of mTORC1. ArfGAP1 interacts with mTORC1 in the absence of amino acids and inhibits mTORC1 lysosomal localization and activation. Mechanistically, the membrane curvature sensing amphipathic lipid packing sensor (ALPS) motifs that bind to vesicle membranes, are crucial for ArfGAP1 to interact with and regulate mTORC1 activity. Importantly, ArfGAP1 represses cell growth through mTORC1 and is an independent prognostic factor for the overall survival of pancreatic cancer patients. Our study identifies ArfGAP1 as a critical regulator of mTORC1 that functions by preventing the lysosomal transport and activation of mTORC1, with potential for cancer therapeutics.
HostingRepository	PRIDE
AnnounceDate	2021-04-01
AnnouncementXML	Submission_2021-04-01_02:38:31.186.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Delong Meng
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-09 01:29:30	ID requested
⏵ 1	2021-04-01 02:38:31	announced

Dataset with its publication pending

submitter keyword: mTORC1, ArfGAP1, amino acid, lysosome, vesicle trafficking

Jenna Lee Jewell
contact affiliation	University of Texas Southwestern Medical Center
contact email	Jenna.Jewell@UTSouthwestern.edu
lab head
Delong Meng
contact affiliation	UTSW
contact email	delongmeng@hotmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024603
     1. Label: PRIDE project
     2. Name: ArfGAP1 inhibits mTORC1 lysosomal localization and activation