PXD026071

PXD026071 is an original dataset announced via ProteomeXchange.

Title	PRMT5-mediated arginine methylation activates AKT kinase to govern tumorigenesis
Description	AKT is involved in a number of key cellular processes including cell proliferation, apoptosis and metabolism. Hyperactivation of AKT is associated with many pathological conditions, particularly cancers. Emerging evidence indicates that arginine methylation is involved in modulating AKT signaling pathway. However, whether and how arginine methylation directly regulates AKT kinase activity remain unknown. Here we report that protein arginine methyltransferase 5 (PRMT5), but not other PRMTs, promotes AKT activation by catalyzing symmetric dimethylation of AKT1 at arginine 391 (R391). Mechanistically, AKT1-R391 methylation cooperates with phosphatidylinositol 3,4,5 trisphosphate (PIP3) to relieve the pleckstrin homology (PH)-in conformation, leading to AKT1 membrane translocation and subsequent activation by phosphoinositide-dependent kinase-1 (PDK1) and the mechanistic target of rapamycin complex 2 (mTORC2). As a result, deficiency in AKT1-R391 methylation significantly suppresses AKT1 kinase activity and tumorigenesis. Lastly, we show that PRMT5 inhibitor synergizes with AKT inhibitor or chemotherapeutic drugs to enhance cell death. Altogether, our study suggests that R391 methylation is an important step for AKT activation and its oncogenic function.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_03:42:30.895.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Bethard
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-18 06:23:41	ID requested
⏵ 1	2022-02-17 03:42:31	announced

Yin S, Liu L, Brobbey C, Palanisamy V, Ball LE, Olsen SK, Ostrowski MC, Gan W, PRMT5-mediated arginine methylation activates AKT kinase to govern tumorigenesis. Nat Commun, 12(1):3444(2021) [pubmed]

submitter keyword: Arginine methylation, PRMT5, AKT, tumorigenesis

Wenjian Gan, Ph.D.
contact affiliation	Department of Biochemistry and Molecular Biology Medical University of South Carolina
contact email	ganw@musc.edu
lab head
Jennifer Bethard
contact affiliation	Medical University of SC
contact email	bethard@musc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026071
     1. Label: PRIDE project
     2. Name: PRMT5-mediated arginine methylation activates AKT kinase to govern tumorigenesis