TY - JOUR
T1 - Calpeptin increases the activity of upstream stimulatory factor and induces high level globin gene expression in erythroid cells
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
Y1 - 2009/7/24
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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U2 - 10.1074/jbc.M109.001461
DO - 10.1074/jbc.M109.001461
M3 - Article
C2 - 19491096
AN - SCOPUS:67749142249
SN - 0021-9258
VL - 284
SP - 20130
EP - 20135
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 30
ER -