FOXO Transcription Factors: Key Targets of the PI3K-Akt Pathway That Regulate Cell Proliferation, Survival, and Organismal Aging

2003 ◽  
pp. 83-90
Author(s):  
Anne Brunet ◽  
Hien Tran ◽  
Michael E. Greenberg
Keyword(s):  
Cell Proliferation ◽  
Transcription Factors ◽  
Akt Pathway ◽  
Foxo Transcription Factors

scholarly journals The IGF-1/PI3K/Akt Pathway Prevents Expression of Muscle Atrophy-Induced Ubiquitin Ligases by Inhibiting FOXO Transcription Factors

2004 ◽  
Vol 14 (3) ◽  
pp. 395-403 ◽  
Author(s):  
Trevor N. Stitt ◽  
Doreen Drujan ◽  
Brian A. Clarke ◽  
Frank Panaro ◽  
Yekatarina Timofeyva ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Muscle Atrophy ◽  
Ubiquitin Ligases ◽  
Akt Pathway ◽  
Foxo Transcription Factors

A novel function of FoxO transcription factors in thrombin-stimulated vascular smooth muscle cell proliferation

2012 ◽  
Vol 108 (07) ◽  
pp. 148-158 ◽  
Author(s):  
Shailaja Mahajan ◽  
Anke Fender ◽  
Jutta Meyer-Kirchrath ◽  
Muhammed Kurt ◽  
Mareike Barth ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
Transcription Factors ◽  
Vascular Smooth Muscle ◽  
Saphenous Vein ◽  
Pi3k Inhibitor Ly294002 ◽  
P27kip1 Protein ◽  
Vein Bypass ◽  
Foxo Transcription Factors

SummaryThrombin exerts coagulation-independent effects on the proliferation and migration of vascular smooth muscle cells (SMC). Forkhead box-O (FoxO) transcription factors regulate cell proliferation, apoptosis and cell cycle arrest, but a possible functional interaction between thrombin and FoxO factors has not been identified to date. In human cultured vascular SMC, thrombin induced a time-dependent phosphorylation of FoxO1 and FoxO3 but not FoxO4. This effect was mimicked by an activating-peptide (AP) for protease-activated receptor (PAR)-1, and abolished by a PAR-1 antagonist (SCH79797). APs for other PARs were without effect. FoxO1 and FoxO3 phosphorylation were prevented by the PI3 kinase (PI3K) inhibitor LY294002 while inhibitors of ERK1/2 (PD98059) or p38MAPK (SB203580) were ineffective. LY294002 moreover prevented thrombin-stimulated SMC mitogenesis and proliferation. FoxO1 and FoxO3 siRNA augmented basal DNA synthesis and proliferation of SMC. Nuclear content of FoxO proteins decreased time-dependently in response to thrombin, coincided with suppressed expression of the cell cycle regulating genes p21CIP1 and p27kip1 by thrombin. FoxO1 siRNA reduced basal p21CIP1 while FoxO3 siRNA attenuated p27kip1 expression; thrombin did not show additive effects. LY294002 restored p21CIP1 and p27kip1 protein expression. Immunohistochemistry revealed that human native and failed saphenous vein grafts were characterised by the cytosolic presence of p-FoxO factors in co-localisation of p21CIP1 and p27kip1 with SMC. In conclusion, thrombin and FoxO factors functionally interact through PI3K/Akt-dependent FoxO phosphorylation leading to expression of cell cycle regulating genes and ultimately SMC proliferation. This may contribute to remodelling and failure of saphenous vein bypass grafts.

scholarly journals The FOXO’s Advantages of Being a Family: Considerations on Function and Evolution

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 787 ◽  
Author(s):  
Michel Schmitt-Ney
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Akt Pathway ◽  
Dna Binding Domain ◽  
Cell Type ◽  
Nematode Caenorhabditis Elegans ◽  
Protein Coding ◽  
C Elegans ◽  
Foxo Transcription Factors

The nematode Caenorhabditis elegans possesses a unique (with various isoforms) FOXO transcription factor DAF-16, which is notorious for its role in aging and its regulation by the insulin-PI3K-AKT pathway. In humans, five genes (including a protein-coding pseudogene) encode for FOXO transcription factors that are targeted by the PI3K-AKT axis, such as in C. elegans. This common regulation and highly conserved DNA-binding domain are the pillars of this family. In this review, I will discuss the possible meaning of possessing a group of very similar proteins and how it can generate additional functionality to more complex organisms. I frame this discussion in relation to the much larger super family of Forkhead proteins to which they belong. FOXO members are very often co-expressed in the same cell type. The overlap of function and expression creates a certain redundancy that might be a safeguard against the accidental loss of FOXO function, which could otherwise lead to disease, particularly, cancer. This is one of the points that will be examined in this “family affair” report.

The Role of Retinoblastoma Protein in Cell Cycle Regulation: An Updated Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Rabih Roufayel ◽  
Rabih Mezher ◽  
Kenneth B. Storey
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Cell Cycle Control ◽  
Expression Of Genes ◽  
E2f Transcription Factor ◽  
Cellular Energetics ◽  
Development And Differentiation ◽  
E2f Transcription Factors ◽  
Rb Phosphorylation

: Selected transcription factors have critical roles to play in organism survival by regulating the expression of genes that control the adaptations needed to handle stress conditions. The retinoblastoma (Rb) protein coupled with the E2F transcription factor family was demonstrated to have roles in controlling the cell cycle during freezing and associated environmental stresses (anoxia, dehydration). Rb phosphorylation or acetylation at different sites provide a mechanism for repressing cell proliferation that is under the control of E2F transcription factors in animals facing stresses that disrupt cellular energetics or cell volume controls. Other central regulators of the cell cycle including Cyclins, Cyclin dependent kinases (Cdks), and checkpoint proteins detect DNA damage or any improper replication, blocking further progression of cell cycle and interrupting cell proliferation. This review provides an insight into the molecular regulatory mechanisms of cell cycle control, focusing on Rb-E2F along with Cyclin-Cdk complexes typically involved in development and differentiation that need to be regulated in order to survive extreme cellular stress.

Sign in / Sign up

Export Citation Format

Share Document