Calpeptin increases the activity of upstream stimulatory factor and induces high level globin gene expression in erythroid cells

I. Ju Lin, Zhuo Zhou, Valerie J. Crusselle-Davis, Babak Moghimi, Kunjal Gandhi, Archana Anantharaman, Dorjan Pantic, Suming Huang, Giridhararao Jayandharan, Li Zhong, Arun Srivastava, Jörg Bungert

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Differentiation of erythroid cells is regulated by cell signaling pathways including those that change the intracellular concentration of calcium. Calcium-dependent proteases have been shown previously to process and regulate the activity of specific transcription factors. We show here that the protein levels of upstream stimulatory factor (USF) increase during differentiation of murine erythroleukemia (MEL) cells. USF was subject to degradation by the Ca2+-dependent protease m-calpain in undifferentiated but not in differentiated MEL cells. Treatment of MEL cells with the specific calpain inhibitor calpeptin increased the levels of USF and strongly induced expression of the adult α- and β-globin genes. The induction of globin gene expression was associated with an increase in the association of USF and RNA polymerase II with regulatory elements of the β-globin gene locus. Calpeptin also induced high level α- and β-globin gene expression in primary CD71-positive erythroid progenitor cells. The combined data suggest that inhibition of calpain activity is required for erythroid differentiation-associated increase in globin gene expression.

Original languageEnglish (US)
Pages (from-to)20130-20135
Number of pages6
JournalJournal of Biological Chemistry
Volume284
Issue number30
DOIs
StatePublished - Jul 24 2009

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Upstream Stimulatory Factors
Erythroid Cells
Globins
Gene expression
Leukemia, Erythroblastic, Acute
Gene Expression
Peptide Hydrolases
Genes
Cell signaling
Calcium
Erythroid Precursor Cells
Calpain
RNA Polymerase II
Transcription Factors
Cells
calpeptin
Association reactions
Degradation
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lin, I. J., Zhou, Z., Crusselle-Davis, V. J., Moghimi, B., Gandhi, K., Anantharaman, A., ... Bungert, J. (2009). Calpeptin increases the activity of upstream stimulatory factor and induces high level globin gene expression in erythroid cells. Journal of Biological Chemistry, 284(30), 20130-20135. https://doi.org/10.1074/jbc.M109.001461
Lin, I. Ju ; Zhou, Zhuo ; Crusselle-Davis, Valerie J. ; Moghimi, Babak ; Gandhi, Kunjal ; Anantharaman, Archana ; Pantic, Dorjan ; Huang, Suming ; Jayandharan, Giridhararao ; Zhong, Li ; Srivastava, Arun ; Bungert, Jörg. / Calpeptin increases the activity of upstream stimulatory factor and induces high level globin gene expression in erythroid cells. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 30. pp. 20130-20135.
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abstract = "Differentiation of erythroid cells is regulated by cell signaling pathways including those that change the intracellular concentration of calcium. Calcium-dependent proteases have been shown previously to process and regulate the activity of specific transcription factors. We show here that the protein levels of upstream stimulatory factor (USF) increase during differentiation of murine erythroleukemia (MEL) cells. USF was subject to degradation by the Ca2+-dependent protease m-calpain in undifferentiated but not in differentiated MEL cells. Treatment of MEL cells with the specific calpain inhibitor calpeptin increased the levels of USF and strongly induced expression of the adult α- and β-globin genes. The induction of globin gene expression was associated with an increase in the association of USF and RNA polymerase II with regulatory elements of the β-globin gene locus. Calpeptin also induced high level α- and β-globin gene expression in primary CD71-positive erythroid progenitor cells. The combined data suggest that inhibition of calpain activity is required for erythroid differentiation-associated increase in globin gene expression.",
author = "Lin, {I. Ju} and Zhuo Zhou and Crusselle-Davis, {Valerie J.} and Babak Moghimi and Kunjal Gandhi and Archana Anantharaman and Dorjan Pantic and Suming Huang and Giridhararao Jayandharan and Li Zhong and Arun Srivastava and J{\"o}rg Bungert",
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Lin, IJ, Zhou, Z, Crusselle-Davis, VJ, Moghimi, B, Gandhi, K, Anantharaman, A, Pantic, D, Huang, S, Jayandharan, G, Zhong, L, Srivastava, A & Bungert, J 2009, 'Calpeptin increases the activity of upstream stimulatory factor and induces high level globin gene expression in erythroid cells', Journal of Biological Chemistry, vol. 284, no. 30, pp. 20130-20135. https://doi.org/10.1074/jbc.M109.001461

Calpeptin increases the activity of upstream stimulatory factor and induces high level globin gene expression in erythroid cells. / Lin, I. Ju; Zhou, Zhuo; Crusselle-Davis, Valerie J.; Moghimi, Babak; Gandhi, Kunjal; Anantharaman, Archana; Pantic, Dorjan; Huang, Suming; Jayandharan, Giridhararao; Zhong, Li; Srivastava, Arun; Bungert, Jörg.

In: Journal of Biological Chemistry, Vol. 284, No. 30, 24.07.2009, p. 20130-20135.

Research output: Contribution to journalArticle

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AU - Lin, I. Ju

AU - Zhou, Zhuo

AU - Crusselle-Davis, Valerie J.

AU - Moghimi, Babak

AU - Gandhi, Kunjal

AU - Anantharaman, Archana

AU - Pantic, Dorjan

AU - Huang, Suming

AU - Jayandharan, Giridhararao

AU - Zhong, Li

AU - Srivastava, Arun

AU - Bungert, Jörg

PY - 2009/7/24

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N2 - Differentiation of erythroid cells is regulated by cell signaling pathways including those that change the intracellular concentration of calcium. Calcium-dependent proteases have been shown previously to process and regulate the activity of specific transcription factors. We show here that the protein levels of upstream stimulatory factor (USF) increase during differentiation of murine erythroleukemia (MEL) cells. USF was subject to degradation by the Ca2+-dependent protease m-calpain in undifferentiated but not in differentiated MEL cells. Treatment of MEL cells with the specific calpain inhibitor calpeptin increased the levels of USF and strongly induced expression of the adult α- and β-globin genes. The induction of globin gene expression was associated with an increase in the association of USF and RNA polymerase II with regulatory elements of the β-globin gene locus. Calpeptin also induced high level α- and β-globin gene expression in primary CD71-positive erythroid progenitor cells. The combined data suggest that inhibition of calpain activity is required for erythroid differentiation-associated increase in globin gene expression.

AB - Differentiation of erythroid cells is regulated by cell signaling pathways including those that change the intracellular concentration of calcium. Calcium-dependent proteases have been shown previously to process and regulate the activity of specific transcription factors. We show here that the protein levels of upstream stimulatory factor (USF) increase during differentiation of murine erythroleukemia (MEL) cells. USF was subject to degradation by the Ca2+-dependent protease m-calpain in undifferentiated but not in differentiated MEL cells. Treatment of MEL cells with the specific calpain inhibitor calpeptin increased the levels of USF and strongly induced expression of the adult α- and β-globin genes. The induction of globin gene expression was associated with an increase in the association of USF and RNA polymerase II with regulatory elements of the β-globin gene locus. Calpeptin also induced high level α- and β-globin gene expression in primary CD71-positive erythroid progenitor cells. The combined data suggest that inhibition of calpain activity is required for erythroid differentiation-associated increase in globin gene expression.

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