Calpeptin Increases the Activity of Upstream Stimulatory Factor and Induces High Level Globin Gene Expression in Erythroid Cells

• Published in: The Journal of biological chemistry Vol. 284; no. 30; pp. 20130 - 20135
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.07.2009; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Calpain - antagonists & inhibitors; Calpain - metabolism; Cell Differentiation; Dipeptides - pharmacology; Enzyme Inhibitors - pharmacology; Erythroid Cells - cytology; Erythroid Cells - metabolism; Female; Gene Expression Regulation; Globins - genetics; Globins - metabolism; Leukemia, Erythroblastic, Acute - genetics; Leukemia, Erythroblastic, Acute - metabolism; Mice; Mice, Inbred C57BL; Molecular Basis of Cell and Developmental Biology; Murinae; Promoter Regions, Genetic; RNA Polymerase II - metabolism; Upstream Stimulatory Factors - genetics; Upstream Stimulatory Factors - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.001461

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 po ly mer ase 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.