FOXO-mediated transcription of cell death genes

Stable Identifier
R-HSA-9614657
Type
Pathway
Species
Homo sapiens
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FOXO transcription factors promote expression of several pro-apoptotic genes, such as FASLG (Brunet et al. 1999, Ciechomska et al. 2003, Chen et al. 2013, Li et al. 2015), PINK1 (Mei et al. 2009, Sengupta et al. 2011), BCL2L11 (BIM) (Gilley et al. 2003, Urbich et al. 2005, Chuang et al. 2007, Hughes et al. 2011, Chen et al. 2013, Wang et al. 2016), BCL6 (Tang et al. 2002, Fernandez de Mattos et al. 2004, Shore et al. 2006) and BBC3 (PUMA) (Dudgeon et al. 2010, Hughes et al. 2011, Liu et al. 2015, Wu et al. 2016, Liu et al. 2017, Fitzwalter et al. 2018). FOXO-mediated induction of cell death genes is important during development, for example during nervous system development, where FOXO promotes neuronal death upon NGF withdrawal (Gilley et al. 2003), and also contributes to the tumor-suppressive role of FOXO factors (Arimoto Ishida et al. 2004). FOXO1 transcriptional activity is implicated in the cell death of enteric nervous system (ENS) precursors. RET signaling, which activates PI3K/AKT signaling, leading to inhibition of FOXO mediated transcription, ensures survival of ENS precursors (Srinivasan et al. 2005).
Transcription of the STK11 (LKB1) gene, encoding Serine/threonine-protein kinase STK11 (also known as Liver kinase B1), which regulates diverse cellular processes, including apoptosis, is directly stimulated by FOXO3 and FOXO4 (Lutzner et al. 2012).

Literature References
PubMed ID Title Journal Year
21164521 NF-Y is essential for expression of the proapoptotic bim gene in sympathetic neurons

Hughes, R, Kristiansen, M, Lassot, I, Desagher, S, Mantovani, R, Ham, J

Cell Death Differ. 2011
26780985 Overexpression of FOXO4 induces apoptosis of clear-cell renal carcinoma cells through downregulation of Bim

Wang, W, Zhou, PH, Hu, W

Mol Med Rep 2016
17667983 Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor

Chuang, PY, Yu, Q, Fang, W, Uribarri, J, He, JC

Kidney Int. 2007
26715362 microRNA-150 promotes cervical cancer cell growth and survival by targeting FOXO4

Li, J, Hu, L, Tian, C, Lu, F, Wu, J, Liu, L

BMC Mol. Biol. 2015
11777915 The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor

Tang, TT, Dowbenko, D, Jackson, A, Toney, L, Lewin, DA, Dent, AL, Lasky, LA

J. Biol. Chem. 2002
28890329 Histone methyltransferase SETDB1 maintains survival of mouse spermatogonial stem/progenitor cells via PTEN/AKT/FOXO1 pathway

Liu, T, Chen, X, Li, T, Li, X, Lyu, Y, Fan, X, Zhang, P, Zeng, W

Biochim Biophys Acta Gene Regul Mech 2017
16943287 Epstein-Barr virus represses the FoxO1 transcription factor through latent membrane protein 1 and latent membrane protein 2A

Shore, AM, White, PC, Hui, RC, Essafi, A, Lam, EW, Rowe, M, Brennan, P

J. Virol. 2006
23707940 miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4

Chen, L, Tang, Y, Wang, J, Yan, Z, Xu, R

Biochem. Biophys. Res. Commun. 2013
15509806 FoxO3a and BCR-ABL regulate cyclin D2 transcription through a STAT5/BCL6-dependent mechanism

Fernández de Mattos, S, Essafi, A, Soeiro, I, Pietersen, AM, Birkenkamp, KU, Edwards, CS, Martino, A, Nelson, BH, Francis, JM, Jones, MC, Brosens, JJ, Coffer, PJ, Lam, EW

Mol. Cell. Biol. 2004
12913110 FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons

Gilley, J, Coffer, PJ, Ham, J

J. Cell Biol. 2003
10102273 Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor

Brunet, A, Bonni, A, Zigmond, MJ, Lin, MZ, Juo, P, Hu, LS, Anderson, MJ, Arden, KC, Blenis, J, Greenberg, ME

Cell 1999
22412893 Gene expression of the tumour suppressor LKB1 is mediated by Sp1, NF-Y and FOXO transcription factors

Lützner, N, De-Castro Arce, J, Rösl, F

PLoS ONE 2012
20978166 PUMA induction by FoxO3a mediates the anticancer activities of the broad-range kinase inhibitor UCN-01

Dudgeon, C, Wang, P, Sun, X, Peng, R, Sun, Q, Yu, J, Zhang, L

Mol. Cancer Ther. 2010
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
14576824 Inhibition of Akt kinase signalling and activation of Forkhead are indispensable for upregulation of FasL expression in apoptosis of glioma cells

Ciechomska, I, Pyrzynska, B, Kazmierczak, P, Kaminska, B

Oncogene 2003
19276113 FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation

Mei, Y, Zhang, Y, Yamamoto, K, Xie, W, Mak, TW, You, H

Proc. Natl. Acad. Sci. U.S.A. 2009
29533771 Autophagy Inhibition Mediates Apoptosis Sensitization in Cancer Therapy by Relieving FOXO3a Turnover

Fitzwalter, BE, Towers, CG, Sullivan, KD, Andrysik, Z, Hoh, M, Ludwig, M, O'Prey, J, Ryan, KM, Espinosa, JM, Morgan, MJ, Thorburn, A

Dev. Cell 2018
25425107 Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress

Liu, ZQ, Shen, M, Wu, WJ, Li, BJ, Weng, QN, Li, M, Liu, HL

Reprod Sci 2015
27730540 Downregulation of Smurf2 ubiquitin ligase in pancreatic cancer cells reversed TGF-β-induced tumor formation

Wu, B, Guo, B, Kang, J, Deng, X, Fan, Y, Zhang, X, Ai, K

Tumour Biol. 2016
15824087 FOXO-dependent expression of the proapoptotic protein Bim: pivotal role for apoptosis signaling in endothelial progenitor cells

Urbich, C, Knau, A, Fichtlscherer, S, Walter, DH, Brühl, T, Potente, M, Hofmann, WK, de Vos, S, Zeiher, AM, Dimmeler, S

FASEB J. 2005
15866051 Enteric neuroblasts require the phosphatidylinositol 3-kinase/Akt/Forkhead pathway for GDNF-stimulated survival

Srinivasan, S, Anitha, M, Mwangi, S, Heuckeroth, RO

Mol. Cell. Neurosci. 2005
14701673 Inhibition of phosphorylation of a forkhead transcription factor sensitizes human ovarian cancer cells to cisplatin

Arimoto-Ishida, E, Ohmichi, M, Mabuchi, S, Takahashi, T, Ohshima, C, Hayakawa, J, Kimura, A, Takahashi, K, Nishio, Y, Sakata, M, Kurachi, H, Tasaka, K, Murata, Y

Endocrinology 2004
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