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Prmt1-mediated translation regulation is a crucial vulnerability of cancer

ABSTRACT: Through an shRNA screen we have identified Prmt1 as a genetic vulnerability of p53/Rb-null murine osteosarcoma cells. Depletion of Prmt1 in p53-deficient cells impairs tumor initiation and maintenance in vitro and in vivo. Mechanistic studies reveal that translation-associated pathways are enriched for Prmt1 downstream targets, implicating a role of Prmt1 in translation control. In particular, we have shown that loss of Prmt1 leads to a the decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. We also observed that p53/Rb-null cells are sensitive to p53-induced translation stress. Analysis of the human tumor cell Achilles data set further reveals that Prmt1 and translation-associated pathways converge on the same functional networks. We propose that targeted therapy directed to inhibition of Prmt1 and its associated translation-related pathways represents a novel and promising therapeutic strategy for p53-deficient cancer cells that exhibit dependencies on translation stress response.

ORGANISM(S): Mus musculus

PROVIDER: GSE93309 | GEO | 2018/01/06

SECONDARY ACCESSION(S): PRJNA360586

REPOSITORIES: GEO

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PRMT1-Mdm4-p53 pathway controls epicardial invasion and cell fate transition

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2020-08-18 | GSE122200 | GEO

Comprehensive transcriptome analysis of the brain in CNS-specific PRMT1 knockout mice.

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Toxoplasma gondii arginine methyltransferase 1 (PRMT1) regulates parasite counting during tachyzoite cell division

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2016-01-14 | E-MTAB-3322 | biostudies-arrayexpress

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