P38{alpha}/JNK Signaling Restrains Erythropoiesis By Suppressing Ezh2-Mediated Epigenetic Silencing of Bim

A remarkable feature of erythropoiesis is the coordination of proliferation, differentiation and apoptosis of erythroid cells to precisely achieve erythropoietic homeostasis to avoid anemia and polycythemia. Anemia is a common disease arising from various causes, including Myelodysplastic syndromes, thalassemia, cancer chemotherapy, chronic kidney disease and hemorrhage. The pro-erythropoietic factor erythropoietin (EPO) is often employed for anemia therapy. However, questions have been raised about the safety of EPO given its potential for tumor promotion in cancer-related anemia. Moreover, many acute and chronic anemias, including hemolysis, sepsis and genetic bone marrow failure diseases such as Diamond-Blackfan anemia are untreatable with EPO. To overcome these hurdles, new molecular mechanisms need to be identified that physiologically restrain erythropoiesis by acting as molecular brakes to prevent over-active erythropoiesis caused by pro-erythropoietic signals. Inhibiting these restraining mechanisms could provide alternative approaches to treat anemia in an EPO-independent fashion. P38 MAPK (Mitogen-activated protein kinase) is an important pathway involved in diverse biological processes. P38 modulates cell proliferation, controls cell survival and decides cell fate during differentiation. P38 pathway functions mainly by phosphorylating and activating important transcription factors in response to different stimuli, including ATF2, CREB, and MEF2. There are four memb...
Source: Blood - Category: Hematology Authors: Tags: 502. Hematopoiesis: Regulation of Gene Transcription, Cytokines, Signal Transduction, Apoptosis, and Cell Cycle Regulation: Poster III Source Type: research