The role of unfolded protein responses in hematopoiesis

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  • MIHARADA Kenichi
    International Research Center for Medical Sciences, Kumamoto University Lund Stem Cell Center, Lund University

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Other Title
  • 異常タンパク質応答と造血制御
  • イジョウ タンパクシツ オウトウ ト ゾウケツ セイギョ

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Abstract

<p>Protein production is tightly regulated in cells because the accumulation of un-/misfolded proteins triggers cellular responses, particularly in the endoplasmic reticulum (ER). Recently, several studies have reported the implications of unfolded protein response (UPR) and ER stress in hematopoiesis, particularly in hematopoietic stem cells (HSCs). The majority of HSCs are maintained in a dormant state under physiological conditions in the adult body, and their protein synthesis rate is also maintained at a low level. Once HSC proliferation is activated, the protein synthesis rate is elevated, and therefore, newly synthesized peptides have to be efficiently folded to prevent the induction of UPR. Importantly, UPR can expand the ER capacity that enables increased protein production and eliminates cells accumulating abnormal proteins; thus, blocking the UPR signal could rather be hazardous for the cells. Thus, understanding how protein quality control is properly controlled and developing methods to manipulate the regulatory mechanisms are imperative to maximize the potential role of HSC.</p>

Journal

  • Rinsho Ketsueki

    Rinsho Ketsueki 63 (9), 1006-1013, 2022

    The Japanese Society of Hematology

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