The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
The Forkhead Transcription Factor FoxO Regulates Transcription of p27 Kip1 and Bim in Response to IL-2
Open accessAbstract
The cytokine IL-2 plays a very important role in the proliferation and survival of activated T cells. These effects of IL-2 are dependent on signaling through the phosphatidylinositol 3-kinase (PI3K) pathway. We and others have shown that PI3K, through activation of protein kinase B/Akt, inhibits transcriptional activation by a number of forkhead transcription factors (FoxO1, FoxO3, and FoxO4). In this study we have investigated the role of these forkhead transcription factors in the IL-2-induced T cell proliferation and survival. We show that IL-2 regulates phosphorylation of FoxO3 in a PI3K-dependent fashion. Phosphorylation and inactivation of FoxO3 appears to play an important role in IL-2-mediated T cell survival, because mere activation of FoxO3 is sufficient to trigger apoptosis in T cells. Indeed, active FoxO3 can induce expression of IL-2-regulated genes, such as the cdk inhibitor p27Kip1 and the proapoptotic Bcl-2 family member Bim. Furthermore, we show that IL-2 triggers a rapid, PI3K-dependent, phosphorylation of FoxO1a in primary T cells. Thus, we propose that inactivation of FoxO transcription factors by IL-2 plays a critical role in T cell proliferation and survival.
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Cites
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Self-citation
Cited by
Dynamic FoxO transcription factors
Huang, H., & Tindall, D. J. (2007) · Journal of Cell Science · doi:10.1242/jcs.001222 · Cited by 1,113
JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis
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FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis
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FOXOs, cancer and regulation of apoptosis
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Metadata
- Authors
- Stahl, M., Dijkers, P. F., Kops, G. J. P. L., Lens, S. M. A., Coffer, P. J., Burgering, B. M. T., & Medema, R. H.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-05
- Volume
- 168
- Issue
- 10
- Pages
- 5024-5031
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2108197605
- Cited by
- 585
- References
- 34
- FWCI
- 11.88
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: The Forkhead Transcription Factor FoxO Regulates Transcription of p27 Kip1 and Bim in Response to IL-2. https://app.cochat.ai/papers/10.4049/jimmunol.168.10.5024
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- Stahl, M., Dijkers, P. F., Kops, G. J. P. L., Lens, S. M. A., Coffer, P. J., Burgering, B. M. T., & Medema, R. H. (2002). The Forkhead Transcription Factor FoxO Regulates Transcription of p27 Kip1 and Bim in Response to IL-2. The Journal of Immunology. https://doi.org/10.4049/jimmunol.168.10.5024
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