CCAAT/enhancer-binding proteins are required for granulopoiesis independent of their induction of the granulocyte colony-stimulating factor receptor.

Blood
Qian-fei Wang, A D Friedman

Abstract

Potential redundancy among members of the CCAAT/enhancer-binding protein (C/EBP) family in myeloid cells is indicated by the ability of C/EBPbeta to replace C/EBPalpha in vivo, by the expression of granulocyte colony-stimulating factor receptor (G-CSFR) on C/EBPalpha(-/-) cell lines, and by our finding that as with C/EBPalpha-estrogen receptor (C/EBPalpha-ER), either C/EBPbeta-ER or C/EBPdelta-ER can induce terminal granulopoiesis in 32D cl3 cells. To assess the consequences of globally inhibiting C/EBPs, we employed KalphaER, containing a Kruppel-associated box (KRAB) transrepression domain, the C/EBPalpha DNA-binding domain, and an ER ligand-binding domain. C/EBPs have a common DNA-binding consensus, and activation of KalphaER repressed transactivation by endogenous C/EBPs 50-fold and reduced endogenous G-CSFR expression. In 32D cl3 cells coexpressing exogenous G-CSFR, activation of KalphaER prevented and even reversed myeloperoxidase, lysozyme, lactoferrin, and C/EBPepsilon RNA induction by G-CSF. In contrast, induction of PU.1 and CD11b, a gene regulated by PU.1 but not by C/EBPs, was unaffected. A KalphaER variant incapable of binding DNA owing to an altered leucine zipper did not affect 32D cl3 differentiation. Transducti...Continue Reading

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Citations

Jul 4, 2002·International Journal of Hematology·Alan D Friedman
Nov 26, 2003·Blood Cells, Molecules & Diseases·Alan D FriedmanRebecca Cleaves
Jun 6, 2006·Nature Immunology·Hideyo HiraiDaniel G Tenen
Jul 31, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nathalie GirardTrang Hoang
Nov 20, 2012·The Journal of Clinical Investigation·Meritxell Alberich-JordàDaniel G Tenen
Dec 19, 2008·PLoS Biology·Andrew B SharabiSi-Yi Chen
Mar 10, 2012·PloS One·Mohamed AbdgawadThomas Hellmark
Mar 16, 2011·Yi chuan = Hereditas·Yun-Zhen Gao, Yu-Chun Pan
Oct 25, 2013·International Journal of Biological Sciences·Kuppusamy Balamurugan, Esta Sterneck
Mar 26, 2013·Cellular and Molecular Life Sciences : CMLS·René HuberKorbinian Brand
May 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·Diana VradiiGary S Stein
Aug 3, 2007·Blood Cells, Molecules & Diseases·Alan D Friedman
Mar 28, 2008·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Satoshi IidaRikiro Fukunaga
Apr 18, 2006·Biochimica Et Biophysica Acta·Mikkel Bruhn Schuster, Bo Torben Porse
Nov 14, 2006·Cancer Cell·Karen KeeshanWarren S Pear
Jan 28, 2005·Leukemia·H LeroyC Preudhomme
Sep 2, 2003·Journal of Leukocyte Biology·Tanawan Kummalue, Alan D Friedman
Feb 14, 2018·Microbiology and Molecular Biology Reviews : MMBR·Shelley M LawrenceVictor Nizet

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