Reactome | FOXO-mediated transcription of cell cycle genes

FOXO-mediated transcription of cell cycle genes

Stable Identifier

R-HSA-9617828

Type

Pathway

Species

Homo sapiens

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FOXO-mediated transcription of cell cycle genes

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FOXO transcription factors induce expression of several genes that negatively regulate proliferation of different cell types, such as erythroid progenitors (Bakker et al. 2004, Wang et al. 2015) and neuroepithelial progenitor cells in the telencephalon (Seoane et al. 2004).
Transcription of cyclin-dependent kinase (CDK) inhibitors CDKN1A (p21Cip1) is directly stimulated by FOXO1, FOXO3 and FOXO4 (Seoane et al. 2004, Tinkum et al. 2013). FOXO transcription factors can cooperate with the SMAD2/3:SMAD4 complex to induce CDKN1A transcription in response to TGF-beta signaling (Seoane et al. 2004).
FOXO transcription factors FOXO1, FOXO3 and FOXO4 stimulate transcription of the CDKN1B (p27Kip1) gene, but direct binding of FOXOs to the CDKN1B gene locus has not been demonstrated (Dijkers et al. 2000, Medema et al. 2000, Lees et al. 2008).
FOXO3 and FOXO4, and possibly FOXO1, directly stimulate transcription of the GADD45A gene (Tran et al. 2002, Furukawa Hibi et al. 2002, Hughes et al. 2011, Sengupta et al. 2011, Ju et al. 2014).
Transcription of the retinoblastoma family protein RBL2 (p130), involved in the maintenance of quiescent (G0) state, is directly stimulated by FOXO1, FOXO3 and FOXO4 (Kops et al. 2002, Chen et al. 2006).
Transcription of the anti-proliferative protein CCNG2 is directly stimulated by FOXO1 and FOXO3, and possibly FOXO4 (Martinez Gac et al. 2004, Chen et al. 2006). Transcription of the anti-proliferative protein BTG1 is directly stimulated by FOXO3 (Bakker et al. 2004, Bakker et al. 2007, Wang et al. 2015).
Transcription of CAV1, encoding caveolin-1, involved in negative regulation of growth factor receptor signaling and establishment of quiescent cell phenotype, is directly stimulated by FOXO1 and FOXO3 (van den Heuvel et al. 2005, Roy et al. 2008, Nho et al. 2013, Sisci et al. 2013).
FOXO1 and FOXO3 promote transcription of the KLF4 gene, encoding a transcription factor Krueppel-like factor 4, which inhibits proliferation of mouse B cells (Yusuf et al. 2008).
FOXO1, together with the p-2S-SMAD2/3:SMAD4 complex, stimulates transcription of the MSTN gene, encoding myostatin, a TGF-beta family member that stimulates differentiation of myoblasts (Allen and Unterman 2007).

Literature References

PubMed ID	Title	Journal	Year
12048180	FOXO forkhead transcription factors induce G(2)-M checkpoint in response to oxidative stress Furukawa-Hibi, Y, Yoshida-Araki, K, Ohta, T, Ikeda, K, Motoyama, N	J. Biol. Chem.	2002
15458387	Direct control of caveolin-1 expression by FOXO transcription factors van den Heuvel, AP, Schulze, A, Burgering, BM	Biochem. J.	2005
16885393	Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors Allen, DL, Unterman, TG	Am. J. Physiol., Cell Physiol.	2007
11884591	Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors Kops, GJ, Medema, RH, Glassford, J, Essers, MA, Dijkers, PF, Coffer, PJ, Lam, EW, Burgering, BM	Mol. Cell. Biol.	2002
24452601	FOXO1-dependent DNA damage repair is regulated by JNK in lung cancer cells Ju, Y, Xu, T, Zhang, H, Yu, A	Int. J. Oncol.	2014
25843800	Knockdown of transcription factor forkhead box O3 (FOXO3) suppresses erythroid differentiation in human cells and zebrafish Wang, H, Li, Y, Wang, S, Zhang, Q, Zheng, J, Yang, Y, Qi, H, Qu, H, Zhang, Z, Liu, F, Fang, X	Biochem. Biophys. Res. Commun.	2015
18787071	Age-dependent FOXO regulation of p27Kip1 expression via a conserved binding motif in rat muscle precursor cells Lees, SJ, Childs, TE, Booth, FW	Am. J. Physiol., Cell Physiol.	2008
18444242	Wild-type APC regulates caveolin-1 expression in human colon adenocarcinoma cell lines via FOXO1a and C-myc Roy, UK, Henkhaus, RS, Ignatenko, NA, Mora, J, Fultz, KE, Gerner, EW	Mol. Carcinog.	2008
14734530	FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1 Bakker, WJ, Blázquez-Domingo, M, Kolbus, A, Besooyen, J, Steinlein, P, Beug, H, Coffer, PJ, Löwenberg, B, von Lindern, M, van Dijk, TB	J. Cell Biol.	2004
17353275	Differential regulation of Foxo3a target genes in erythropoiesis Bakker, WJ, van Dijk, TB, Parren-van Amelsvoort, M, Kolbus, A, Yamamoto, K, Steinlein, P, Verhaak, RG, Mak, TW, Beug, H, Löwenberg, B, von Lindern, M	Mol. Cell. Biol.	2007
16493026	FOXO transcription factors cooperate with delta EF1 to activate growth suppressive genes in B lymphocytes Chen, J, Yusuf, I, Andersen, HM, Fruman, DA	J. Immunol.	2006
21159781	FoxO transcription factors promote cardiomyocyte survival upon induction of oxidative stress Sengupta, A, Molkentin, JD, Paik, JH, DePinho, RA, Yutzey, KE	J. Biol. Chem.	2011
15084259	Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation Seoane, J, Le, HV, Shen, L, Anderson, SA, Massague, J	Cell	2004
18375530	KLF4 is a FOXO target gene that suppresses B cell proliferation Yusuf, I, Kharas, MG, Chen, J, Peralta, RQ, Maruniak, A, Sareen, P, Yang, VW, Kaestner, KH, Fruman, DA	Int. Immunol.	2008
11964479	DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein Tran, H, Brunet, A, Grenier, JM, Datta, SR, Fornace, AJ, DiStefano, PS, Chiang, LW, Greenberg, ME	Science	2002
11094066	Forkhead transcription factor FKHR-L1 modulates cytokine-dependent transcriptional regulation of p27(KIP1) Dijkers, PF, Medema, RH, Pals, C, Banerji, L, Thomas, NS, Lam, EW, Burgering, BM, Raaijmakers, JA, Lammers, JW, Koenderman, L, Coffer, PJ	Mol. Cell. Biol.	2000
23580232	FoxO3a (Forkhead Box O3a) deficiency protects Idiopathic Pulmonary Fibrosis (IPF) fibroblasts from type I polymerized collagen matrix-induced apoptosis via caveolin-1 (cav-1) and Fas Nho, RS, Peterson, M, Hergert, P, Henke, CA	PLoS ONE	2013
21196578	FoxO1 and SIRT1 regulate beta-cell responses to nitric oxide Hughes, KJ, Meares, GP, Hansen, PA, Corbett, JA	J. Biol. Chem.	2011
10783894	AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1 Medema, RH, Kops, GJ, Bos, JL, Burgering, BM	Nature	2000
23918930	Forkhead box O1 (FOXO1) protein, but not p53, contributes to robust induction of p21 expression in fasted mice Tinkum, KL, White, LS, Marpegan, L, Herzog, E, Piwnica-Worms, D, Piwnica-Worms, H	J. Biol. Chem.	2013
14966295	Control of cyclin G2 mRNA expression by forkhead transcription factors: novel mechanism for cell cycle control by phosphoinositide 3-kinase and forkhead Martínez-Gac, L, Marqués, M, García, Z, Campanero, MR, Carrera, AC	Mol. Cell. Biol.	2004
24047697	The estrogen receptor α is the key regulator of the bifunctional role of FoxO3a transcription factor in breast cancer motility and invasiveness Sisci, D, Maris, P, Cesario, MG, Anselmo, W, Coroniti, R, Trombino, GE, Romeo, F, Ferraro, A, Lanzino, M, Aquila, S, Maggiolini, M, Mauro, L, Morelli, C, Andó, S	Cell Cycle	2013