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Caspase-dependent apoptosis by ectopic expression of E2F-4

Oncogene volume 19, pages 4713–4720 (2000)Cite this article

Abstract

E2F is a family of transcription factors which regulates cell cycle and apoptosis of mammalian cells. E2F-1-3 localize in the nucleus, and preferentially bind pRb, while E2F-4 and 5 have no nuclear localization signal and preferentially bind p107/p130. E2F-6 suppresses the transcriptional activity of other E2F proteins. DP-1 and 2 are heterodimeric partners of each E2F protein. Using tetracycline-responsive promoters, here we compared the effects of ectopic expression of E2F-1, DP-1 and E2F-4 on cell cycle progression and apoptosis in Chinese hamster cell lines. We found that E2F-4, as well as DP-1 and E2F-1, induced growth arrest and caspase-dependent apoptosis. E2F-4 did not have a marked effect on cell cycle progression, while E2F-1 induced DNA synthesis of resting cells and DP-1 arrested cells in G1. Ectopic expression of E2F-4 did not activate E2F-dependent transcription. Our results suggest that expression of E2F-4 at elevated levels induces growth arrest and apoptosis of mammalian cells through a mechanism distinct from E2F-1 and DP-1.

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Acknowledgements

We are grateful to H Bujard (Universität Heidelberg, Germany), C-L Wu, E Harlow (MGH Cancer Center, Boston, USA) and K Helin (European Institute of Oncology, Milan, Italy) for providing plasmids and antibodies. This work is in part supported by American Cancer Research Faculty Award to NH Heintz, the Vermont Cancer Center, the Lake Champlain Cancer Research Organization, and NIH grant #GM54726 to NH Heintz and by Center of Excellence grant from STA, Japan to Y Mitsui, and a project grant to K Saida and Y Mitsui of Research and Development for the Elucidation of Biological Functions from the Ministry of International Trade and Industry of Japan.

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Authors and Affiliations

  1. Department of Pathology, University of Vermont College of Medicine, Burlington, 05403, Vermont, VT, USA

    Young-Chae Chang, Sharon Illenye, Nicholas H Heintz & Junji Magae

  2. National Institute of Bioscience and Human-Technology, 1-1 Higashi, Tsukuba, 305-8566, Japan

    Young-Chae Chang, Yun-Sik Lee, Kaname Saida, Youji Mitsui & Junji Magae

  3. Second Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, 602, Japan

    Hiroo Nakajima, Tazuko Makiyama, Ikuya Fujiwara, Naruhiko Mizuta & Kiyoshi Sawai

  4. Institute of Research and Innovation, 1201 Takada, Kashiwa, 277-0861, Japan

    Nobuko Honjo & Junji Magae

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Chang, YC., Nakajima, H., Illenye, S. et al. Caspase-dependent apoptosis by ectopic expression of E2F-4. Oncogene 19, 4713–4720 (2000). https://doi.org/10.1038/sj.onc.1203833

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