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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4437-4444.
Prepublished online as a Blood First Edition Paper on January 21, 2005; DOI 10.1182/blood-2004-08-2976.
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Submitted August 2, 2004
Accepted January 2, 2005
TEF, an anti-apoptotic bZIP transcription factor related to the oncogenic E2A-HLF chimera, inhibits cell growth by down regulating expression of the common  chain of cytokine receptors
Takeshi Inukai*, Toshiya Inaba, Jinjun Dang, Ryoko Kuribara, Keiya Ozawa, Atsushi Miyajima, Wenshu Wu, A T Look, Yojiro Arinobu, Hiromi Iwasaki, Koichi Akashi, Keiko Kagami, Kumiko Goi, Kanji Sugita, and Shinpei Nakazawa
Department of Pediatrics, School of Medicine, University of Yamanashi, Yamanashi, Japan
Department of Molecular Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
Department of Experimental Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
Division of Hematology, Jichi Medical School, Tochigi, Japan
Institute of Molecular and Cellular Bioscience, University of Tokyo, Tokyo, Japan
Pediatric Oncology Department, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Department of Experimental Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; Pediatric Oncology Department, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
* Corresponding author; email: tinukai{at}res.yamanashi-med.ac.jp.
Gain and/or loss of function mediated by chimeric transcription factors generated by nonrandom translocations in leukemia is a key to understanding oncogenesis. E2A-hepatic leukemia factor (HLF), a chimeric leucine zipper (bZIP) transcription factor expressed in t(17;19)-positive leukemia cells, contributes to leukemogenesis through its potential to inhibit apoptosis. To identify physiological counterparts of this chimera, we investigated the function of other bZIP factors that bind to the same DNA sequence recognized by E2A-HLF. Here, we show that thyrotroph embryonic factor (TEF), which shares a high level of sequence identity with HLF and recognizes the same DNA sequence, is expressed in a small fraction of each subset of hematolymphoid progenitors. When TEF was introduced into FL5.12 interleukin (IL)-3-dependent cells, TEF protected the cells from apoptosis due to IL-3 deprivation. Unexpectedly, TEF also almost completely downregulated expression of the common  (c) chain of cytokine receptors. Consequently, TEF-expressing cells accumulated in G0/G1 phase without undergoing apoptosis. These findings suggest that TEF is one of the apoptotic regulators in hematopoietic progenitors and controls hematopoietic cell proliferation by regulating the expression of the c chain. In contrast, E2A-HLF promoted cell survival more efficiently than TEF, but did not downregulate c chain expression, suggesting that E2A-HLF retains ideal properties for driving leukemic transformation.
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