Document Detail


Stress granules contribute to α-globin homeostasis in differentiating erythroid cells.
MedLine Citation:
PMID:  22452989     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hemoglobin is the major biosynthetic product of developing erythroid cells. Assembly of hemoglobin requires the balanced production of globin proteins and the oxygen-carrying heme moiety. The heme-regulated inhibitor kinase (HRI) participates in this process by phosphorylating eIF2α and inhibiting the translation of globin proteins when levels of free heme are limiting. HRI is also activated in erythroid cells subjected to oxidative stress. Phospho-eIF2α-mediated translational repression induces the assembly of stress granules (SG), cytoplasmic foci that harbor untranslated mRNAs and promote the survival of cells subjected to adverse environmental conditions. We have found that differentiating erythroid, but not myelomonocytic or megakaryocytic, murine and human progenitor cells assemble SGs, in vitro and in vivo. Targeted knockdown of HRI or G3BP, a protein required for SG assembly, inhibits spontaneous and arsenite-induced assembly of SGs in erythroid progenitor cells. This is accompanied by reduced α-globin production and increased apoptosis suggesting that G3BP+ SGs facilitate the survival of developing erythroid cells.
Authors:
Laura Ghisolfi; Shilpee Dutt; Marie E McConkey; Benjamin L Ebert; Paul Anderson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-20
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  420     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-23     Completed Date:  2012-06-22     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  768-74     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Carrier Proteins / genetics,  metabolism
Cells, Cultured
Cytoplasmic Granules / metabolism,  physiology*
Erythroid Cells / cytology*,  metabolism
Erythropoiesis*
Homeostasis*
Humans
Mice
Mice, Inbred BALB C
Transcription, Genetic
alpha-Globins / biosynthesis*,  genetics
eIF-2 Kinase / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
P01 AI065858/AI/NIAID NIH HHS; P01 AI065858-01A1/AI/NIAID NIH HHS; R01 HL082945/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/G3BP protein, human; 0/alpha-Globins; EC 2.7.11.1/eIF-2 Kinase
Comments/Corrections

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