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Similar but distinct effects of the tristetraprolin/TIS11 immediate-early proteins on cell survival

Oncogene volume 19, pages 1657–1664 (2000)Cite this article

Abstract

The immediate early protein tristetraprolin (TTP) is required to prevent inappropriate production of the cytokine TNF-α, and is a member of a zinc finger protein family that is associated with RNA binding. TTP expression is induced by TNF-α, and evidence indicates that TTP can bind and destabilize the TNF-α mRNA. TTP and the closely related TIS11b and TIS11d proteins are evolutionarily conserved, however, and induced transiently in various cell types by numerous diverse stimuli, suggesting that they have additional functions. Supporting this idea, continuous expression of each TTP/TIS11 protein at physiological levels causes apoptotic cell death. By various criteria, this cell death appears analogous to apoptosis induced by certain oncoproteins. It is also dependent upon the zinc fingers, suggesting that it involves action on appropriate cellular targets. TTP but not TIS11b or TIS11d also sensitizes cells to induction of apoptosis by TNF-α. The data suggest that the TTP and TIS11 immediate early proteins have similar but distinct effects on growth or survival pathways, and that TTP might influence TNF-α regulation at multiple levels.

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Acknowledgements

We thank Mark Worthington for the TTP (Nup475) cDNA, Harvey Herschman for TIS11b and TIS11d cDNAs, and Vishva Dixit for the CrmA expression construct. For helpful discussions and reagents we are grateful to Junying Yuan and Karl Munger, whom we also thank for critically reading this manuscript along with Yang Shi and Blackwell lab members. This work was supported by a fellowship from the Arthritis Foundation to BA Johnson, and by grants from the US Army Breast Cancer Program (17-94-J-4063) and the NIH (PO1 HD17461).

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  1. Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachusetts, MA, USA

    Barbra A Johnson, Mayya Geha & T Keith Blackwell

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  1. Barbra A Johnson
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  2. Mayya Geha
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  3. T Keith Blackwell
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Johnson, B., Geha, M. & Blackwell, T. Similar but distinct effects of the tristetraprolin/TIS11 immediate-early proteins on cell survival. Oncogene 19, 1657–1664 (2000). https://doi.org/10.1038/sj.onc.1203474

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