Forkhead box O (FoxO) transcription factors are downstream targets of the serine/threonine protein kinase B (PKB)/Akt. The Akt kinase regulates processes of cellular proliferation and survival. Phosphorylation of FoxOs by Akt inhibits transcriptional functions of FoxOs and contributes to cell survival, growth and proliferation. Emerging evidence suggests involvement of FoxOs in diverse intracellular signaling pathways with critical roles in a number of physiological as well as pathological conditions including cancer. The FoxO signaling is regulated by their interactions with other intracellular proteins as well as their post-translational modifications such as phosphorylation. FoxOs promote cell growth inhibitory and/or apoptosis signaling by either inducing expression of multiple pro-apoptotic members of the Bcl2-family of mitochondria-targeting proteins, stimulating expression of death receptor ligands such as Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), or enhancing levels of various cyclin-dependent kinase inhibitors (CDKIs). Coupled with their ability to cross-talk with p53, FoxOs represent an important class of tumor suppressors in a variety of cancers. This review summarizes our current understanding of mechanisms by which Akt and FoxOs regulate cell growth and survival that in turn offers opportunities for development of novel strategies to combat cancer. This article is part of a Special Issue entitled: P13K-AKT-FOxO axis in cancer and aging.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbamcr.2011.03.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The role of insulin signaling with FOXO and FOXK transcription factors.
Endocr J
October 2024
Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Insulin is an essential hormone for animal activity and survival, and it controls the metabolic functions of the entire body. Throughout the evolution of metazoan animals and the development of their brains, a sustainable energy supply has been essential to overcoming the competition for survival under various environmental stresses. Managing energy for metabolism, preservation, and consumption inevitably involves high oxidative stress, causing tissue damage in various organs.
View Article and Find Full Text PDFThe influence of uremic toxins on low bone turnover disease in chronic kidney disease.
Tzu Chi Med J
December 2023
Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.
Uremic toxins play a crucial role in the development of low bone turnover disease in chronic kidney disease (CKD) through the induction of oxidative stress. This oxidative stress disrupts the delicate balance between bone formation and resorption, resulting in a decline in both bone quantity and quality. Reactive oxygen species (ROS) activate nuclear factor kappa-B and mitogen-activated protein kinase signaling pathways, promoting osteoclastogenesis.
View Article and Find Full Text PDFTranscriptional dysregulation of autophagy in the muscle of a mouse model of Duchenne muscular dystrophy.
Sci Rep
January 2024
Department of Pharmacology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo, 060-8556, Japan.
It has been reported that autophagic activity is disturbed in the skeletal muscles of dystrophin-deficient mdx mice and patients with Duchenne muscular dystrophy (DMD). Transcriptional regulations of autophagy by FoxO transcription factors (FoxOs) and transcription factor EB (TFEB) play critical roles in adaptation to cellular stress conditions. Here, we investigated whether autophagic activity is dysregulated at the transcription level in dystrophin-deficient muscles.
View Article and Find Full Text PDFGaining insight into the role of FoxO1 in the progression of disuse-induced skeletal muscle atrophy.
Adv Biol Regul
August 2022
Department of Paediatrics, University of Oxford, Children's Hospital, John Radcliffe, Oxford, OX3 9DU, UK; Institute of Developmental and Regenerative Medicine, Roosevelt Dr, IMS-Tetsuya Nakamura Building, Oxford, OX3 7TY, UK; MDUK Oxford Neuromuscular Centre, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK. Electronic address:
Expression of FoxO transcription factors increases during certain forms of atrophy. In a dephosphorylated state, FoxOs participate in ubiquitin-mediated proteasomal degradation through the transcriptional activation of E3-ubiquitin ligases such as MAFbx/atrogin-1 and MuRF1. There is exhaustive research demonstrating that FoxO3a is sufficient to induce MAFbx/atrogin-1 and MuRF-1 expressions.
View Article and Find Full Text PDFThe Akt Forkhead Box O Transcription Factor Axis Regulates Human Cytomegalovirus Replication.
mBio
August 2022
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center- Shreveport, Shreveport, Louisiana, USA.
Article Synopsis
- - The protein kinase Akt plays a crucial role in various cellular processes, and its inhibition can trigger herpesviruses to reactivate from latency, indicating that decreased Akt activity might encourage lytic replication.
- - During human cytomegalovirus (HCMV) infection, Akt is found in an inactive state within fibroblasts, linked to specific changes in phosphorylation patterns and the localization of the substrate FoxO3a, while mTORC1 activation further contributes to Akt inactivation.
- - Unexpectedly, maintaining active Akt (myr-Akt) reduces viral replication, revealing that the inactivation of Akt is necessary for efficient HCMV replication, primarily through the involvement of FoxO3a.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!