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Scientific article
English

Regulation of calreticulin expression during induction of differentiation in human myeloid cells. Evidence for remodeling of the endoplasmic reticulum

Published inThe Journal of biological chemistry, vol. 277, no. 35, p. 32369-32378
Publication date2002
Abstract

Induction of differentiation of HL-60 human myeloid cells profoundly affected expression of calreticulin, a Ca(2+)-binding endoplasmic reticulum chaperone. Induction with Me(2)SO or retinoic acid reduced levels of calreticulin protein by approximately 60% within 4 days. Pulse-chase studies indicated that labeled calreticulin decayed at similar rates in differentiated and undifferentiated cells (t(12) approximately 4.6 days), but the biosynthetic rate was <10% of control after 4 days. Differentiation also induced a rapid decline in calreticulin mRNA levels (90% reduction after 1 day) without a decrease in transcript stability (t(12) approximately 5 h). Nuclear run-on analysis demonstrated rapid down-regulation of gene transcription (21% of control at 2 h). Differentiation also greatly reduced the Ca(2+) content of the cells (25% of control), although residual Ca(2+) pools remained sensitive to thapsigargin, ionomycin, and inositol trisphosphate. Progressive decreases were also observed in levels of calnexin and ERp57, whereas BiP/GRP78 and protein disulfide isomerase were only modestly affected. Ultrastructural studies showed a substantial reduction in endoplasmic reticulum content of the cells. Thus, terminal differentiation of myeloid cells was associated with decreased endoplasmic reticulum content, selective reductions in molecular chaperones, and diminished intracellular Ca(2+) stores, perhaps reflecting an endoplasmic reticulum remodeling program as a prominent feature of granulocytic differentiation.

Keywords
  • Calcium-Binding Proteins/ genetics
  • Calreticulin
  • Cell Differentiation/ physiology
  • Cell Line
  • Endoplasmic Reticulum/metabolism
  • Gene Expression Regulation, Neoplastic/drug effects
  • HL-60 Cells
  • Humans
  • Kinetics
  • Molecular Chaperones/genetics
  • RNA, Messenger/genetics
  • Ribonucleoproteins/ genetics
  • Sulfuric Acid Esters/pharmacology
  • Time Factors
  • Transcription, Genetic/drug effects
  • Tretinoin/pharmacology
Affiliation Not a UNIGE publication
Citation (ISO format)
CLARK, R. A. et al. Regulation of calreticulin expression during induction of differentiation in human myeloid cells. Evidence for remodeling of the endoplasmic reticulum. In: The Journal of biological chemistry, 2002, vol. 277, n° 35, p. 32369–32378. doi: 10.1074/jbc.M205269200
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ISSN of the journal0021-9258
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