Dataset Information

PRMT5-mediated arginine methylation activates AKT kinase to govern tumorigenesis

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell

SUBMITTER: Jennifer Bethard

LAB HEAD: Wenjian Gan, Ph.D.

PROVIDER: PXD026071 | Pride | 2022-02-17

REPOSITORIES: Pride

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Publications

PRMT5-mediated arginine methylation activates AKT kinase to govern tumorigenesis.

Yin Shasha S Liu Liu L Brobbey Charles C Palanisamy Viswanathan V Ball Lauren E LE Olsen Shaun K SK Ostrowski Michael C MC Gan Wenjian W

Nature communications 20210608 1

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, promo ...[more]

PMID: 34103528

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			Action	DRS
	110819_WenjianGan_AKT1.msf	Msf
	110819_WenjianGan_AKT1.raw	Raw
	AKT1.fasta	Fasta
	Methyl__R_Sites.txt	Txt
	checksum.txt	Txt