A role for intracellular and extracellular DEK in regulating hematopoiesis

Curr Opin Hematol. 2017 Jul;24(4):300-306. doi: 10.1097/MOH.0000000000000344.

Abstract

Purpose of review: Hematopoietic stem/progenitor cell fate decision during hematopoiesis is regulated by intracellular and extracellular signals such as transcription factors, growth factors, and cell-to-cell interactions. In this review, we explore the function of DEK, a nuclear phosphoprotein, on gene regulation. We also examine how DEK is secreted and internalized by cells, and discuss how both endogenous and extracellular DEK regulates hematopoiesis. Finally, we explore what currently is known about the regulation of DEK during inflammation.

Recent findings: DEK negatively regulates the proliferation of early myeloid progenitor cells but has a positive effect on the differentiation of mature myeloid cells. Inflammation regulates intracellular DEK concentrations with inflammatory stimuli enhancing DEK expression. Inflammation-induced nuclear factor-kappa B activation is regulated by DEK, resulting in changes in the production of other inflammatory molecules such as IL-8. Inflammatory stimuli in turn regulates DEK secretion by cells of hematopoietic origin. However, how inflammation-induced expression and secretion of DEK regulates hematopoiesis remains unknown.

Summary: Understanding how DEK regulates hematopoiesis under both homeostatic and inflammatory conditions may lead to a better understanding of the biology of HSCs and HPCs. Furthering our knowledge of the regulation of hematopoiesis will ultimately lead to new therapeutics that may increase the efficacy of hematopoietic stem cell transplantation.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Self Renewal
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Extracellular Space / metabolism
  • Gene Expression Regulation
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Intracellular Space / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Poly-ADP-Ribose Binding Proteins

Substances

  • Chromosomal Proteins, Non-Histone
  • DEK protein, human
  • Oncogene Proteins
  • Poly-ADP-Ribose Binding Proteins