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Mitogen-activated protein kinases (MAPKs) are inactivated by dual-specificity phosphatases (DUSPs), the activities of which are tightly regulated during cell differentiation. Using knockdown screening and single-cell transcriptional analysis, we demonstrate that DUSP4 is the phosphatase that specifically inactivates p38 kinase to promote megakaryocyte (Mk) differentiation. Mechanistically, PRMT1-mediated methylation of DUSP4 triggers its ubiquitinylation by an E3 ligase HUWE1. Interestingly, the mechanistic axis of the DUSP4 degradation and p38 activation is also associated with a transcriptional signature of immune activation in Mk cells. In the context of thrombocytopenia observed in myelodysplastic syndrome (MDS), we demonstrate that high levels of p38 MAPK and PRMT1 are associated with low platelet counts and adverse prognosis, while pharmacological inhibition of p38 MAPK or PRMT1 stimulates megakaryopoiesis. These findings provide mechanistic insights into the role of the PRMT1-DUSP4-p38 axis on Mk differentiation and present a strategy for treatment of thrombocytopenia associated with MDS.
Pubmed ID: 34320342 RIS Download
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A freely accessible on-line systems biology resource devoted to all aspects of protein modification, as well as other post-translational modifications. It provides valuable and unique tools for both cell biologists and mass spectroscopists. PhosphoSite is a human- and mouse-centric database. It includes features such as: viewing the locations of modified residues on molecular models; browsing and searching MS2 records by disease, tissue, and cell line; submitting lists of peptides to identify previously reported genes; searching by sub-cellular localization, treatment, tissues, cell types, cell lines and diseases, and protein types and protein domains; searching for experimentally-verified kinase substrates and viewing preferred substrate motifs; and viewing MS2 spectra for peptides and sites not previously published.
View all literature mentionsRegistry and results database of federally and privately supported clinical trials conducted in United States and around world. Provides information about purpose of trial, who may participate, locations, and phone numbers for more details. This information should be used in conjunction with advice from health care professionals.Offers information for locating federally and privately supported clinical trials for wide range of diseases and conditions. Research study in human volunteers to answer specific health questions. Interventional trials determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments. Observational trials address health issues in large groups of people or populations in natural settings. ClinicalTrials.gov contains trials sponsored by National Institutes of Health, other federal agencies, and private industry. Studies listed in database are conducted in all 50 States and in 178 countries.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsWeb based interface for exploring and analyzing a comprehensive maize-specific cross-platform expression compendium. This compendium was constructed by collecting, homogenizing and formally annotating publicly available microarrays from Gene Expression Omnibus (GEO), and ArrayExpress.
View all literature mentionsA software which acquires and processes data sets, primarily through the Xcalibur system.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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