Gadd34 requirement for normal hemoglobin synthesis

Andrew D. Patterson, M. Christine Hollander, Georgina F. Miller, Albert J. Fornace

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The protein encoded by growth arrest and DNA damage-inducible transcript 34 (Gadd34) is associated with translation initiation regulation following certain stress responses. Through interaction with the protein phosphatase 1 catalytic subunit (PP1c), Gadd34 recruits PP1c for the removal of an inhibitory phosphate group on the α subunit of elongation initiation factor 2, thereby reversing the shutoff of protein synthesis initiated by stress-inducible kinases. In the absence of stress, the physiologic consequences of Gadd34 function are not known. Initial analysis of Gadd34-null mice revealed several significant findings, including hypersplenism, decreased erythrocyte volume, increased numbers of circulating erythrocytes, and decreased hemoglobin content, resembling some thalassemia syndromes. Biochemical analysis of the hemoglobin-producing reticulocyte (an erythrocyte precursor) revealed that the decreased hemoglobin content in the Gadd34-null erythrocyte is due to the reduced initiation of the globin translation machinery. We propose that an equilibrium state exists between Gadd34/PP1c and the opposing heme-regulated inhibitor kinase during hemoglobin synthesis in the reticulocyte.

Original languageEnglish (US)
Pages (from-to)1644-1653
Number of pages10
JournalMolecular and cellular biology
Volume26
Issue number5
DOIs
StatePublished - Mar 1 2006

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DNA Damage
Hemoglobins
Protein Phosphatase 1
Growth
Reticulocytes
Phosphotransferases
Prokaryotic Initiation Factor-2
Erythrocytes
Peptide Elongation Factor 2
Erythrocyte Volume
Hypersplenism
Erythrocyte Count
Thalassemia
Globins
Heme
Proteins
Phosphates

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Patterson, Andrew D. ; Hollander, M. Christine ; Miller, Georgina F. ; Fornace, Albert J. / Gadd34 requirement for normal hemoglobin synthesis. In: Molecular and cellular biology. 2006 ; Vol. 26, No. 5. pp. 1644-1653.
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Gadd34 requirement for normal hemoglobin synthesis. / Patterson, Andrew D.; Hollander, M. Christine; Miller, Georgina F.; Fornace, Albert J.

In: Molecular and cellular biology, Vol. 26, No. 5, 01.03.2006, p. 1644-1653.

Research output: Contribution to journalArticle

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AU - Fornace, Albert J.

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