C/EBPα in normal and malignant myelopoiesis

International Journal of Hematology
Alan D Friedman

Abstract

CCAAT/enhancer binding protein α (C/EBPα) dimerizes via its leucine zipper (LZ) domain to bind DNA via its basic region and activate transcription via N-terminal trans-activation domains. The activity of C/EBPα is modulated by several serine/threonine kinases and via sumoylation, its gene is activated by RUNX1 and additional transcription factors, its mRNA stability is modified by miRNAs, and its mRNA is subject to translation control that affects AUG selection. In addition to inducing differentiation, C/EBPα inhibits cell cycle progression and apoptosis. Within hematopoiesis, C/EBPα levels increase as long-term stem cells progress to granulocyte-monocyte progenitors (GMP). Absence of C/EBPα prevents GMP formation, and higher levels are required for granulopoiesis compared to monopoiesis. C/EBPα interacts with AP-1 proteins to bind hybrid DNA elements during monopoiesis, and induction of Gfi-1, C/EBPε, KLF5, and miR-223 by C/EBPα enables granulopoiesis. The CEBPA ORF is mutated in approximately 10 % of acute myeloid leukemias (AML), leading to expression of N-terminally truncated C/EBPαp30 and C-terminal, in-frame C/EBPαLZ variants, which inhibit C/EBPα activities but also play additional roles during myeloid transformation. RU...Continue Reading

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Citations

Mar 11, 2015·International Journal of Hematology·Tomohiko Tamura
Oct 30, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yong XiePeifu Tang
Jul 15, 2015·Biochemical and Biophysical Research Communications·Akihiro TamuraTaira Maekawa
Jun 18, 2016·Blood·Elisabeth F Heuston
Jun 30, 2016·Antioxidants & Redox Signaling·Sashwati Roy
Nov 5, 2016·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Yimei DaiWenqing Zhang
May 20, 2017·International Journal of Hematology·Akihiro TamuraYoshiyuki Kosaka
Nov 18, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Wei ChenYi-Ping Li
Apr 11, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Luxiang WangJun Zhu
Aug 1, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hong GuoAlan D Friedman
Apr 30, 2019·Critical Reviews in Biotechnology·Matías Gutiérrez-GonzálezClaudia Altamirano
Apr 20, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Xinxin WangXiang Gao
May 24, 2019·PloS One·Lei PengAlan D Friedman
Apr 3, 2020·Biomolecular NMR Assignments·Andras LangChristoph Wiedemann
May 6, 2015·Cancer Science·Hideyo HiraiTaira Maekawa
Jun 30, 2018·International Journal of Hematology·Hisashi Takei, Susumu S Kobayashi
Oct 4, 2018·Frontiers in Immunology·Bronson R WestonJohn J Tyson
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Sep 2, 2017·BMC Musculoskeletal Disorders·Xinxin WangXiang Gao
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Jan 13, 2021·The Journal of Biological Chemistry·Zhibin HuangYiyue Zhang
May 26, 2020·Pharmacology & Therapeutics·Bao-Chun JiangYong-Jing Gao
Apr 6, 2021·PLoS Computational Biology·Claude GérardFrédéric P Lemaigre

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