PXD031543

PXD031543 is an original dataset announced via ProteomeXchange.

Title	Quantitative Phosphoproteomic Analyses Identify STK11IP as a Lysosome-Specific Substrate of mTORC1 that Regulates Lysosomal Acidification
Description	The evolutionarily conserved serine/threonine kinase mTORC1 is a central regulator of cell growth and proliferation. mTORC1 is activated on the lysosome surface. However, once mTORC1 is activated, it is unclear whether mTORC1 phosphorylates local lysosomal proteins to regulate specific aspects of lysosomal biology. By integrating analyses of lysosome proteome with mTORC1-regulated phosphoproteome, we identify STK11IP as a lysosome-specific substrate of mTORC1. mTORC1 phosphorylates STK11IP at S404. Knockout of STK11IP leads to a robust increase of autophagy flux. Dephosphorylation of STK11IP at S404 represses the role of STK11IP as an autophagy inhibitor. Mechanistically, STK11IP binds to V-ATPase, and regulates the activity of V-ATPase. Knockout of STK11IP protects mice from fasting or Methionine/Choline-Deficient Diet diet-induced fatty liver. Thus, our study demonstrates that STK11IP phosphorylation represents a novel mechanism for mTORC1 to regulate lysosomal acidification and autophagy, and points to STK11IP as a promising therapeutic target for the amelioration of diseases with aberrant autophagy signaling.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-20_06:28:21.379.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xu-Dong Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue; phosphorylated residue
Instrument	LTQ Orbitrap Velos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-09 07:55:54	ID requested
⏵ 1	2022-05-20 06:28:22	announced

Zi Z, Zhang Z, Feng Q, Kim C, Wang XD, Scherer PE, Gao J, Levine B, Yu Y, Quantitative phosphoproteomic analyses identify STK11IP as a lysosome-specific substrate of mTORC1 that regulates lysosomal acidification. Nat Commun, 13(1):1760(2022) [pubmed]

submitter keyword: Phosphoproteomics STK11IP

Yonghao Yu
contact affiliation	Department of biochemistry, UT Southwestern Medical Center
contact email	yonghao.yu@utsouthwestern.edu
lab head
Xu-Dong Wang
contact affiliation	UT Southwestern Medical Center
contact email	Xu-Dong.Wang@utsouthwestern.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031543
     1. Label: PRIDE project
     2. Name: Quantitative Phosphoproteomic Analyses Identify STK11IP as a Lysosome-Specific Substrate of mTORC1 that Regulates Lysosomal Acidification