PXD037078

PXD037078 is an original dataset announced via ProteomeXchange.

Title	Rheb and TRF1 PhastID mass spectrometric data
Description	Rheb is a small G protein that functions as the direct activator of the mechanistic target of rapamycin complex 1 (mTORC1) to coordinate signaling cascades in response to nutrients and growth factors. Despite extensive studies, the guanine nucleotide exchange factor (GEF) that directly activates Rheb remains unclear, at least in part due to the dynamic and transient nature of protein-protein interactions (PPIs) that are the hallmarks of signal transduction. Here, we report the development of a rapid and robust proximity labeling system named Pyrococcus horikoshii biotin protein ligase (PhBPL)-assisted biotin identification (PhastID) and detail the insulin-stimulated changes in Rheb-proximity protein networks that were identified using PhastID. In particular, we found that the lysosomal V-ATPase subunit ATP6AP1 could dynamically interact with Rheb. ATP6AP1 could directly bind to Rheb through its last 12 amino acids and utilizes a tri-aspartate motif in its highly conserved C-tail to enhance Rheb GTP loading. In fact, targeting the ATP6AP1 C-tail could block Rheb activation and inhibit cancer cell proliferation and migration. Our findings highlight the versatility of PhastID in mapping transient PPIs in live cells, reveal ATP6AP1's role as an unconventional GEF for Rheb, and underscore the importance of ATP6AP1 in integrating mTORC1 activation signals through Rheb, filling in the missing link in Rheb/mTORC1 activation.
HostingRepository	iProX
AnnounceDate	2022-09-29
AnnouncementXML	Submission_2025-02-05_19:13:23.085.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xinyu Hou
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite; TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-29 20:44:52	ID requested
⏵ 1	2025-02-05 19:13:24	announced

Feng R, Liu F, Li R, Zhou Z, Lin Z, Lin S, Deng S, Li Y, Nong B, Xia Y, Li Z, Zhong X, Yang S, Wan G, Ma W, Wu S, Songyang Z, The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb. Cell Res, 34(5):355-369(2024) [pubmed]

submitter keyword: Rheb, PhastID

Songyang Zhou
contact affiliation	Sun Yat-Sen University
contact email	songyanz@mail.sysu.edu.cn
lab head
Xinyu Hou
contact affiliation	Sun Yat-Sen University
contact email	houxy26@mail2.sysu.edu.cn
dataset submitter

iProX dataset URI