The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
FOXO3 induces FOXO1-dependent autophagy by activating the AKT1 signaling pathway
Open accessAbstract
Forkhead box O (FOXO) transcriptional protein family members, including FOXO1 and FOXO3, are involved in the modulation of autophagy. However, whether there is redundancy between FOXO1 and FOXO3 in the ability to induce autophagy remains unclear. In this study, we showed that FOXO3 induced a transcription-dependent autophagy, and FOXO1 was required for this process. Overexpression of wild-type FOXO3 (WT) or FOXO3 (3A), which harbors alanine mutations at residues Thr32, Ser253 and Ser315, but not transcription-inactive FOXO3 (∆DB3A), significantly induced autophagy in the human embryonic kidney cell line HEK293T and mouse embryonic fibroblast (MEF) cell lines. Interestingly, depletion of FOXO1 by siRNA attenuated FOXO3-induced autophagy. Our data also showed that FOXO3 overexpression did not increase the expression of FOXO1 at the protein level, although FOXO3 was capable of binding the promoter region of FOXO1 and inducing an increase in the transcription of FOXO1 mRNA. Furthermore, our results showed that FOXO3 promoted the translocation of FOXO1 from the nucleus to the cytoplasm, resulting in an increase in FOXO1-induced autophagy. Moreover, our results supported a mechanism whereby FOXO3 dramatically increased the expression of the class I PtdIns3K catalytic subunit PIK3CA, leading to an increase in AKT1 activity, which resulted in the phosphorylation and nuclear export of FOXO1. To the best of our knowledge, our data are the first to suggest that FOXO1 plays a central role in FOXO3-induced autophagy.
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Cites
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
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Protein modules and signalling networks
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FoxO3 Controls Autophagy in Skeletal Muscle In Vivo
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Cited by
The interplay of ROS and the PI3K/Akt pathway in autophagy regulation
Kma, L., & Baruah, T. J. (2022) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.2104 · Cited by 394
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FOXO transcription factor family in cancer and metastasis
Jiramongkol, Y., & Lam, E. W.-F. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09883-w · Cited by 281
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Metadata
- Authors
- Zhou, J., Liao, W., Yang, J., Ma, K., Li, X., Wang, Y., Wang, D., Wang, L., Zhang, Y., Yin, Y., Zhao, Y., & Zhu, W.-G.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2012-12
- Volume
- 8
- Issue
- 12
- Pages
- 1712-1723
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- OpenAlex
- W1997730267
- Cited by
- 192
- References
- 13
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Zhou, J., Liao, W., Yang, J., Ma, K., Li, X., Wang, Y., Wang, D., Wang, L., Zhang, Y., Yin, Y., Zhao, Y., & Zhu, W.-G. (2012). FOXO3 induces FOXO1-dependent autophagy by activating the AKT1 signaling pathway. Autophagy. https://doi.org/10.4161/auto.21830
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