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E2F2 converts reversibly differentiated PC12 cells to an irreversible, neurotrophin-dependent state

Oncogene volume 20, pages 5124–5131 (2001)Cite this article

Abstract

E2Fs play a central role in cell proliferation and growth arrest through their ability to regulate genes involved in cell cycle progression, arrest and apoptosis. Recent studies further indicate that this family of transcriptional regulators participate in cell fate/differentiation events. They are thus likely to have a prominent role in controlling the terminal differentiation process and its irreversibility. Here we have specifically examined the role of E2F2 in neuronal differentiation using a gain-of-function approach. Endogenous E2F2 increased in PC12 cells in response to nerve growth factor (NGF) and was also expressed in cerebellar granule neurons undergoing terminal differentiation. While PC12 cells normally undergo reversible dedifferentiation and cell cycle re-entry upon NGF removal, forced expression of E2F2 inhibited these events and induced apoptosis. Thus, E2F2 converted PC12-derived neurons from a reversible to a ‘terminally’ differentiated, NGF-dependent state, analogous to postmitotic sympathetic neurons. This contrasts with the effects of E2F4, which enhances the differentiation state of PC12 cells without affecting cell cycle parameters or survival. These results indicate that E2F2 may have a unique role in maintaining the postmitotic state of terminally differentiated neurons, and may participate in apoptosis in neurons attempting to re-enter the cell cycle. It may also be potentially useful in promoting the terminally arrested/differentiated state of tumor cells.

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Acknowledgements

This work was made possible by PHS grants DK36468 and CA-79999 as well as an Annual Research Award from the Worcester Foundation for Biomedical Research to DL Kilpatrick.

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  1. Stephan P Persengiev

    Present address: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, Massachusetts, USA

Authors and Affiliations

  1. Department of Cellular and Molecular Physiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, Massachusetts, USA

    Stephan P Persengiev, Junqing Li, Matthew L Poulin & Daniel L Kilpatrick

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  1. Stephan P Persengiev
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  2. Junqing Li
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  4. Daniel L Kilpatrick
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Correspondence to Daniel L Kilpatrick.

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Persengiev, S., Li, J., Poulin, M. et al. E2F2 converts reversibly differentiated PC12 cells to an irreversible, neurotrophin-dependent state. Oncogene 20, 5124–5131 (2001). https://doi.org/10.1038/sj.onc.1204663

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