EDAG mediates Hsp70 nuclear localization in erythroblasts and rescues dyserythropoiesis in myelodysplastic syndrome

• DOI: 10.1096/fj.201902946r
• Publication Date: 2020-04-30T02:35:41Z
• Authors: Xiao‐Ming Dong; Ke Zhao; Wei‐Wei Zheng; Cheng‐Wang Xu; Mei‐Jiang Zhang; Rong‐Hua Yin; Rui Gao; Liu‐jun Tang; Jin‐Fang Liu; Hui Chen; Yi‐Qun Zhan; Miao Yu; Chang‐Hui Ge; Hui‐Ying Gao; Xiu Li; Teng Luo; Hong‐Mei Ning; Xiao‐Ming Yang; Chang‐Yan Li
• Keywords: Cell Nucleus; Cytoplasm; 0303 health sciences; Erythroblasts; Caspase 3; Nuclear Proteins; Apoptosis; Cell Differentiation; Hematologic Diseases; 03 medical and health sciences; Gene Expression Regulation; Myelodysplastic Syndromes; Humans; Erythropoiesis; HSP70 Heat-Shock Proteins; Cells, Cultured

During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of to localize was found in Myelodysplastic syndrome (MDS) erythroblasts can induce dyserythropoiesis, with arrest maturation death erythroblasts. However, mechanism nuclear trafficking remains unknown. Here, we hematopoietic transcriptional regulator, EDAG, be a novel binding partner that forms protein complex during normal differentiation. EDAG overexpression blocked cytoplasmic translocation induced by EPO deprivation, inhibited degradation, thereby promoting an Hsp70-dependent manner. Furthermore, myelodysplastic patients is dramatically down-regulated, forced expression has been restore localization elevate level significant extent. In addition, rescued dyserythropoiesis MDS increasing differentiation decreasing cell apoptosis. This study demonstrates molecular sustaining establishes might suitable therapeutic target for patients.