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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