RGD Reference Report - Protein arginine methyltransferase 1 interacts with and activates p38alpha to facilitate erythroid differentiation. - Rat Genome Database

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Protein arginine methyltransferase 1 interacts with and activates p38alpha to facilitate erythroid differentiation.

Authors: Hua, WK  Chang, YI  Yao, CL  Hwang, SM  Chang, CY  Lin, WJ 
Citation: Hua WK, etal., PLoS One. 2013;8(3):e56715. doi: 10.1371/journal.pone.0056715. Epub 2013 Mar 6.
RGD ID: 10047341
Pubmed: (View Article at PubMed) PMID:23483889
DOI: Full-text: DOI:10.1371/journal.pone.0056715

Protein arginine methylation is emerging as a pivotal posttranslational modification involved in regulating various cellular processes; however, its role in erythropoiesis is still elusive. Erythropoiesis generates circulating red blood cells which are vital for body activity. Deficiency in erythroid differentiation causes anemia which compromises the quality of life. Despite extensive studies, the molecular events regulating erythropoiesis are not fully understood. This study showed that the increase in protein arginine methyltransferase 1 (PRMT1) levels, via transfection or protein transduction, significantly promoted erythroid differentiation in the bipotent human K562 cell line as well as in human primary hematopoietic progenitor CD34(+) cells. PRMT1 expression enhanced the production of hemoglobin and the erythroid surface marker glycophorin A, and also up-regulated several key transcription factors, GATA1, NF-E2 and EKLF, which are critical for lineage-specific differentiation. The shRNA-mediated knockdown of PRMT1 suppressed erythroid differentiation. The methyltransferase activity-deficient PRMT1G80R mutant failed to stimulate differentiation, indicating the requirement of arginine methylation of target proteins. Our results further showed that a specific isoform of p38 MAPK, p38alpha, promoted erythroid differentiation, whereas p38beta did not play a role. The stimulation of erythroid differentiation by PRMT1 was diminished in p38alpha- but not p38beta-knockdown cells. PRMT1 appeared to act upstream of p38alpha, since expression of p38alpha still promoted erythroid differentiation in PRMT1-knockdown cells, and expression of PRMT1 enhanced the activation of p38 MAPK. Importantly, we showed for the first time that PRMT1 was associated with p38alpha in cells by co-immunoprecipitation and that PRMT1 directly methylated p38alpha in in vitro methylation assays. Taken together, our findings unveil a link between PRMT1 and p38alpha in regulating the erythroid differentiation program and provide evidence suggesting a novel regulatory mechanism for p38alpha through arginine methylation.


Gene Ontology Annotations    

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Prmt1  (protein arginine methyltransferase 1)

Additional Information