title: MASL1 induces erythroid differentiation in human erythropoietin-dependent CD34+ cells through the Raf/MEK/ERK pathway.
abstract: Human erythropoiesis is a dynamic and complex multistep process involving differentiation of early erythroid progenitors into enucleated RBCs. The mechanisms underlying erythropoiesis still remain incompletely understood. We previously demonstrated that erythropoietin-stimulated clone-1, which is selectively expressed in normal human erythroid-lineage cells, shares 99.5% identity with malignant fibrous histiocytoma-amplified sequences with leucine-rich tandem repeats 1 (MASL1). In this study, we hypothesized that the MASL1 gene plays a role in erythroid differentiation, and used a human erythroid cell culture system to explore this concept. MASL1 mRNA and protein expression levels were significantly increased during the erythroid differentiation of CD34(+) cells following erythropoietin (EPO) treatment. Conversely, MASL1 knockdown reduced erythroid differentiation in EPO-treated CD34(+) cells. In addition, MASL1 knockdown interrupted the Raf/MEK/ERK signaling pathway in CD34(+) cells. MASL1 mutant-transfected CD34(+) cells also showed decreased erythroid differentiation. Furthermore, inhibition of the SH3 domain of Son of Sevenless, which is an upstream adapter protein in EPO-induced erythroid differentiation, also reduced MASL1 expression and phosphorylation of Raf/MEK/ERK kinases that consequently reduced erythroid differentiation of EPO-induced CD34(+) cells. Importantly, we also demonstrated that MASL1 interacts physically with Raf1. Taken together, our data provide novel insights into MASL1 regulation of erythropoiesis through the Raf/MEK/ERK pathway.
authors: Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Chutima
authors: C
authors: Kumkhaek
authors: Wulin
authors: W
authors: Aerbajinai
authors: Wenli
authors: W
authors: Liu
authors: Jianqiong
authors: J
authors: Zhu
authors: Naoya
authors: N
authors: Uchida
authors: Roger
authors: R
authors: Kurlander
authors: Matthew M
authors: MM
authors: Hsieh
authors: John F
authors: JF
authors: Tisdale
authors: Griffin P
authors: GP
authors: Rodgers
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis; D004921:Erythropoietin / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020664:Son of Sevenless Proteins / Q000378:metabolism; D015854:Up-Regulation; D048490:raf Kinases / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C117302:MFHAS1 protein, human; D015513:Oncogene Proteins; D012333:RNA, Messenger; D020664:Son of Sevenless Proteins; D004921:Erythropoietin; D048490:raf Kinases