Browsing by Author "Saha, Anjan K."

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    Concise Review: A Role for DEK in Stem/Progenitor Cell Biology
    (Oxford University Press, 2013) Broxmeyer, Hal E.; Mor-Vaknin, Nirit; Kappes, Ferdinand; Legendre, Maureen; Saha, Anjan K.; Ou, Xuan; O’Leary, Heather; Capitano, Maegan; Cooper, Scott; Markovitz, David M.; Microbiology and Immunology, School of Medicine
    Understanding the factors that regulate hematopoiesis opens up the possibility of modifying these factors and their actions for clinical benefit. DEK, a non-histone nuclear phosphoprotein initially identified as a putative proto-oncogene, has recently been linked to regulate hematopoiesis. DEK has myelosuppressive activity in vitro on proliferation of human and mouse hematopoietic progenitor cells and enhancing activity on engraftment of long-term marrow repopulating mouse stem cells, has been linked in coordinate regulation with the transcription factor C/EBPα, for differentiation of myeloid cells, and apparently targets a long-term repopulating hematopoietic stem cell for leukemic transformation. This review covers the uniqueness of DEK, what is known about how it now functions as a nuclear protein and also as a secreted molecule that can act in paracrine fashion, and how it may be regulated in part by dipeptidylpeptidase 4, an enzyme known to truncate and modify a number of proteins involved in activities on hematopoietic cells. Examples are provided of possible future areas of investigation needed to better understand how DEK may be regulated and function as a regulator of hematopoiesis, information possibly translatable to other normal and diseased immature cell systems.
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    Secreted nuclear protein DEK regulates hematopoiesis through CXCR2 signaling
    (American Society for Clinical Investigation, 2019-05-20) Capitano, Maegan L.; Mor-Vaknin, Nirit; Saha, Anjan K.; Cooper, Scott; Legendre, Maureen; Guo, Haihong; Contreras-Galindo, Rafael; Kappes, Ferdinand; Sartor, Maureen A.; Lee, Christopher T.; Huang, Xinxin; Markovitz, David M.; Broxmeyer, Hal E.; Microbiology and Immunology, School of Medicine
    The nuclear protein DEK is an endogenous DNA-binding chromatin factor regulating hematopoiesis. DEK is one of only 2 known secreted nuclear chromatin factors, but whether and how extracellular DEK regulates hematopoiesis is not known. We demonstrated that extracellular DEK greatly enhanced ex vivo expansion of cytokine-stimulated human and mouse hematopoietic stem cells (HSCs) and regulated HSC and hematopoietic progenitor cell (HPC) numbers in vivo and in vitro as determined both phenotypically (by flow cytometry) and functionally (through transplantation and colony formation assays). Recombinant DEK increased long-term HSC numbers and decreased HPC numbers through a mechanism mediated by the CXC chemokine receptor CXCR2 and heparan sulfate proteoglycans (HSPGs) (as determined utilizing Cxcr2-/- mice, blocking CXCR2 antibodies, and 3 different HSPG inhibitors) that was associated with enhanced phosphorylation of ERK1/2, AKT, and p38 MAPK. To determine whether extracellular DEK required nuclear function to regulate hematopoiesis, we utilized 2 mutant forms of DEK: one that lacked its nuclear translocation signal and one that lacked DNA-binding ability. Both altered HSC and HPC numbers in vivo or in vitro, suggesting the nuclear function of DEK is not required. Thus, DEK acts as a hematopoietic cytokine, with the potential for clinical applicability.