N-terminal region of CCAAT/enhancer-binding protein epsilon is critical for cell cycle arrest, apoptosis, and functional maturation during myeloid differentiation

The Journal of Biological Chemistry
H NakajimaMakoto Handa

Abstract

CCAAT/enhancer-binding protein epsilon (C/EBPepsilon) plays a critical role in terminal myeloid differentiation. Differentiation is an integrated process of cell cycle arrest, morphological change, functional maturation, and apoptosis. However, the molecular networks underlying these events in C/EBPepsilon-induced differentiation remain poorly understood. To reveal these mechanisms, we performed a detailed molecular analysis of C/EBPepsilon-induced differentiation using an inducible form of C/EBPepsilon. The activation of C/EBPepsilon induced growth arrest, morphological differentiation, the expression of CD11b and secondary granule proteins, and apoptosis in myeloid cell lines. Unlike C/EBPalpha, C/EBPepsilon dramatically up-regulated p27 with a concomitant down-regulation of cdk4/6 and cyclin D2/A/E. Moreover, the anti-apoptotic proteins Bcl-2 and Bcl-x were down-regulated, whereas pro-apoptotic protein Bax remained unchanged. Using a variety of mutants, we revealed that these events were all regulated by the N-terminal activation domain of C/EBPepsilon. Interestingly, some of the differentiation processes such as the induction of secondary granule protein genes were clearly inhibited by c-Myc; however, inhibition of apoptosi...Continue Reading

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Citations

Apr 27, 2010·Annual Review of Nutrition·Noa Noy
Jul 5, 2013·PloS One·Carolyn GlassArchibald Perkins
Mar 26, 2013·Cellular and Molecular Life Sciences : CMLS·René HuberKorbinian Brand
Nov 27, 2015·BMC Immunology·Corinna Cavan PedersenJack Bernard Cowland
Jan 17, 2015·Journal of Translational Medicine·Francesco ChiappelliCarl A Maida
Jan 9, 2014·Blood·Maria T LarsenJack B Cowland
Jun 26, 2015·Journal of Biomolecular Screening·Hanna S RadomskaSusumu S Kobayashi
Feb 14, 2018·Microbiology and Molecular Biology Reviews : MMBR·Shelley M LawrenceVictor Nizet
Aug 26, 2016·Immunological Reviews·Jack B Cowland, Niels Borregaard
Sep 8, 2009·Cell Biology International·Yukihiro FurusawaTakashi Kondo
Sep 24, 2020·Cancers·Beiyuan Liang, Jing Wang
Sep 26, 2009·Biochemical and Biophysical Research Communications·Hideaki NakajimaToshio Kitamura

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