Abstract
The promotion of cellular survival, dedifferentiation, and uncontrolled proliferation via the suppression of apoptotic effectors is a fundamental characteristic of tumor cells. As substrates that are negatively regulated by oncogenic signaling cascades driven by AKT, SGK (serum- and glucocorticoid-inducible kinase), IkB kinase (IKK), ERK, and cyclin-dependent kinases (CDK), forkhead box-class O (FOXO) transcription factors have emerged as bona fide tumor suppressors. These transcription factors indeed regulate a variety of cellular responses and themselves are regulated by reversible phosphorylation, acetylation, ubiquitination and miRNAs. This review will discuss our current understanding of mechanisms for FOXO regulation and the potential implications for therapeutically restoring FOXO transcriptional activity.
Keywords: Apoptosis, FOXO, TRAIL, BIM, PP2A, proteasome, 14-3-3, micro RNA, PI3K, AKT, MIRNA, VELCADE, PS-341
Current Drug Targets
Title: Harnessing the Tumor Suppressor Function of FOXO as an Alternative Therapeutic Approach in Cancer
Volume: 12 Issue: 9
Author(s): Amrik Singh, Jessica Plati and Roya Khosravi-Far
Affiliation:
Keywords: Apoptosis, FOXO, TRAIL, BIM, PP2A, proteasome, 14-3-3, micro RNA, PI3K, AKT, MIRNA, VELCADE, PS-341
Abstract: The promotion of cellular survival, dedifferentiation, and uncontrolled proliferation via the suppression of apoptotic effectors is a fundamental characteristic of tumor cells. As substrates that are negatively regulated by oncogenic signaling cascades driven by AKT, SGK (serum- and glucocorticoid-inducible kinase), IkB kinase (IKK), ERK, and cyclin-dependent kinases (CDK), forkhead box-class O (FOXO) transcription factors have emerged as bona fide tumor suppressors. These transcription factors indeed regulate a variety of cellular responses and themselves are regulated by reversible phosphorylation, acetylation, ubiquitination and miRNAs. This review will discuss our current understanding of mechanisms for FOXO regulation and the potential implications for therapeutically restoring FOXO transcriptional activity.
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Cite this article as:
Singh Amrik, Plati Jessica and Khosravi-Far Roya, Harnessing the Tumor Suppressor Function of FOXO as an Alternative Therapeutic Approach in Cancer, Current Drug Targets 2011; 12 (9) . https://dx.doi.org/10.2174/138945011796150271
DOI https://dx.doi.org/10.2174/138945011796150271 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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