FOXO3 induces FOXO1-dependent autophagy by activating the AKT1 signaling pathway

Abstract

Abbreviations: ATG, autophagy related; FOXO1, forkhead box O1; FOXO3, forkhead box O3; GFP, green fluorescent protein; MAP1LC3, microtubule-associated protein 1 light chain 3; PIK3CA, class I PI3K catalytic subunit the BECN1-PtdIns3K complex to promote autophagosome formation. 16,17 Recent evidence has revealed that the FOXO protein family members FOXO1 and FOXO3 promote autophagy. [18][19][20][21][22][23] In skeletal muscle cells, FOXO3 directly upregulates autophagy-related genes, such as microtubule-associated protein 1 light chain 3 (MAP1LC3) and BCL2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3).19 FOXO1 has both transcription-dependent and transcription-independent roles in autophagy. In mouse cardiomyocytes, FOXO1 is deacetylated by the NAD-dependent deacetylase sirtuin-1 (SIRT1) that, in turn, induces the expression of the RAS-related GTP-binding protein RAB7A, which mediates the fusion of mature autophagic vesicles with lysosomes. 21 In addition, FOXO1 mediates starvation-induced autophagy through a transcription-independent mechanism in human cancer cells. We have previously observed that cytoplasmic FOXO1 is required for serum starvation-or H 2 O 2 -induced autophagy in cancer cells. Under these conditions, FOXO1 became acetylated and dissociated from SIRT2 in the cytoplasm, and the acetylated FOXO1, in turn, binds to ATG7 to promote autophagy. 23 Therefore, it is ©2012 Landes Bioscience. Do not distribute.www.landesbioscience.com Autophagy

Tregs restrain dendritic cell autophagy to ameliorate autoimmunity

“…Our findings provide evidence for a CTLA4-mediated transcriptional-dependent regulation of autophagy in DCs though activation of the PI3K/Akt axis that results in nuclear exclusion of FoxO1 and decreased transcription of Lc3b. Nuclear presence of FoxO1 is a prerequisite for transcriptional activation of autophagy genes in a process that is controlled by Akt (55). In line with this, another member of the FoxO family, FoxO3, has been shown to transactivate the expression of the Lc3 gene in cardiomyocytes (56).…”

“…In line with this, another member of the FoxO family, FoxO3, has been shown to transactivate the expression of the Lc3 gene in cardiomyocytes (56). However, it was later delineated that FoxO3 upregulated the PI3K/Akt pathway, which phosphorylated FoxO1 and mediated FoxO1 shuttling from the nucleus (55). Interestingly, and in contrast with our results, earlier reports showed that CTLA4 binding induced FoxO3 nuclear localization in DCs (57, 58), but both studies did not provide a linear relationship between CTLA4 engagement and FoxO3 nuclear localization in DCs.…”

Overexpression of microRNA-96-5p inhibits autophagy and apoptosis and enhances the proliferation, migration and invasiveness of human breast cancer cells

“…It is expressed at low levels within breast cancer cells and exhibits the ability to affect the translation of forkhead box protein O1 (FOXO1) and FOXO3 (34,(38)(39)(40)(41). Additionally, evidence has revealed that FOXO1 regulates autophagy (42)(43)(44)(45)(46)(47)(48)(49). Primarily, the present study hypothesized that connections exist between miR-96 and autophagy, and that the likely target protein of this interaction is FOXO1.…”

Autocrine VEGF maintains endothelial survival through regulation of metabolism and autophagy

“…FOXO transcription factors are known to regulate mitochondrial function (Ferber et al, 2012), cell metabolism (Hirota et al, 2008) and autophagy (Zhou et al, 2012;Zhao et al, 2007) in several cell types, but these effects of FOXO have not been clearly linked to VEGF signaling in the endothelium. Only recently, VEGF-mediated activation of cell surface receptors has been associated with suppression of FOXO1 (Zhuang et al, 2013).…”