Abstract
Hematopoietic stem cells (HSCs) are responsible for the production of blood cells throughout the human lifespan. Single HSCs can give rise to at least eight distinct blood-cell lineages. Together, hematopoiesis, erythropoiesis, and angiogenesis coordinate several biological processes, i.e., cellular interactions during development and proliferation, guided migration, lineage programming, and reprogramming by transcription factors. Any dysregulation of these processes can result in hematological disorders and/or malignancies. Several studies of the molecular mechanisms governing HSC maintenance have demonstrated that protein regulation by the ubiquitin proteasomal pathway is crucial for normal HSC function. Recent studies have shown that reversal of ubiquitination by deubiquitinating enzymes (DUBs) plays an equally important role in hematopoiesis; however, information regarding the biological function of DUBs is limited. In this review, we focus on recent discoveries about the physiological roles of DUBs in hematopoiesis, erythropoiesis, and angiogenesis and discuss the DUBs associated with common hematological disorders and malignancies, which are potential therapeutic drug targets.
Highlights
Blood consists of red blood cells (RBCs), megakaryocytes, myeloid cells and lymphocytes
Definitive erythropoiesis is initiated in bone marrow in successive waves of erythroid progenitor-cell maturation, including generation of burst-forming unit erythroids, colony-forming unit erythroids (CFU-Es), proerythroblasts, and basophilic, polychromatic, and orthochromatic erythroblasts derived from hematopoietic stem cells (HSCs) [5,6]
Rehman et al reported the discovery of a new family of deubiquitinating enzymes (DUBs) called MINDY, which shows high selectivity for cleavage of K48-linked polyubiquitin chains [29]
Summary
Blood consists of red blood cells (RBCs), megakaryocytes, myeloid cells (monocytes/macrophages and neutrophils) and lymphocytes All these components are produced by rare cells in the bone marrow called hematopoietic stem cells (HSCs) through a process known as hematopoiesis [1]. Mesodermal cells in the embryo form aggregates of endothelial precursor cells or angioblasts called blood islands [9,10]. These blood islands fuse to form hierarchical networks of arteries, capillaries, and veins, whereas HSCs mature to form the components of blood [9]. HSC differentiation is a tightly controlled process, and recent studies suggest that post-translational modification of protein substrates plays an essential role in its regulation. Normal hematopoiesis requires tight regulation of the expression of lineage-specific genes and of epigenetic and post-translational modifications, and any perturbations in this process may result in myeloid or lymphoid disorders or malignancies [1]
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