JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation Journal Article


Authors: Liu, F.; Zhao, X.; Perna, F.; Wang, L.; Koppikar, P.; Abdel-Wahab, O.; Harr, M. W.; Levine, R. L.; Xu, H.; Tefferi, A.; Deblasio, A.; Hatlen, M.; Menendez, S.; Nimer, S. D.
Article Title: JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation
Abstract: The JAK2V617F constitutively activated tyrosine kinase is found in most patients with myeloproliferative neoplasms. While examining the interaction between JAK2 and PRMT5, an arginine methyltransferase originally identified as JAK-binding protein 1, we found that JAK2V617F (and JAK2K539L) bound PRMT5 more strongly than did wild-type JAK2. These oncogenic kinases also acquired the ability to phosphorylate PRMT5, greatly impairing its ability to methylate its histone substrates, and representing a specific gain-of-function that allows them to regulate chromatin modifications. We readily detected PRMT5 phosphorylation in JAK2V617F-positive patient samples, and when we knocked down PRMT5 in human CD34+ cells using shRNA, we observed increased colony formation and erythroid differentiation. These results indicate that phosphorylation of PRMT5 contributes to the mutant JAK2-induced myeloproliferative phenotype. © 2011 Elsevier Inc.
Journal Title: Cancer Cell
Volume: 19
Issue: 2
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2011-02-15
Start Page: 283
End Page: 294
Language: English
DOI: 10.1016/j.ccr.2010.12.020
PROVIDER: scopus
PUBMED: 21316606
PMCID: PMC4687747
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 4 March 2011" - "CODEN: CCAEC" - "Source: Scopus"
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MSK Authors
  1. Stephen D Nimer
    347 Nimer
  2. Ross Levine
    620 Levine
  3. Xinyang Zhao
    29 Zhao
  4. Fabiana Perna
    45 Perna
  5. Michael Harr
    5 Harr
  6. Lan Wang
    14 Wang
  7. Fan Rong Liu
    16 Liu
  8. Megan A Hatlen
    14 Hatlen
  9. Hao Xu
    5 Xu