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Small-Molecule Inhibition of PRMT5 Induces Translational Stress and p53 in JAK2V617F Mutant Myeloproliferative Neoplasms

Sonderegger, Stefan; Cerruti, Loretta; Tremblay, Cedric; Toulmin, Emma; Saw, Jesslyn; Nebl, Thomas; Hannan, Katherine; Lane, Steven W.; Falk, Hendrik; Unnikrishnan, Ashwin; Stupple, Paul


Background: Myeloproliferative neoplasms (MPN) are a diverse group of hematopoietic stem cell disorders. JAK2V617F gain-of-function is the most prevalent mutation, accounting for more than 60% of MPNs. PRMT5 was initially identified as a JAK-binding protein. Its enzymatic function catalyses the symmetric di-methylation of arginine on a variety of substrates, including histones and proteins of the splicing apparatus. It has been proposed that mutant JAK2 can phosphorylate PRMT5, leading to loss...[Show more]

CollectionsANU Research Publications
Date published: 2018
Type: Journal article
Source: Blood
DOI: 10.1182/blood-2018-99-118406


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