| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Published online before print May 22, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Department of Physiological Chemistry and Center for Biomedical Genetics, University Medical Center Utrecht, The Netherlands; and
Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam
Correspondence: René H. Medema, Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. E-mail: r.medema{at}nki.nl
Forkhead transcription factors of the FOXO family are important downstream targets of protein kinase B (PKB)/Akt, a kinase shown to play a decisive role in cell proliferation and cell survival. Direct phosphorylation by PKB/Akt inhibits transcriptional activation by FOXO factors, causing their displacement from the nucleus into the cytoplasm. Work from recent years has shown that this family of transcription factors regulates the expression of a number of genes that are crucial for the proliferative status of a cell, as well as a number of genes involved in programmed cell death. As such, these transcription factors appear to play an essential role in many of the effects of PKB/Akt on cell proliferation and survival. Indeed, in cells of the hematopoietic system, mere activation of a FOXO factor is sufficient to activate a variety of proapoptotic genes and to trigger apoptosis. In contrast, in most other cell types, activation of FOXO blocks cellular proliferation and drives cells into a quiescent state. In such cell types, FOXO factors also provide the protective mechanisms that are required to adapt to the altered metabolic state of quiescent cells. Thus, as PKB/Akt signaling is switched off, FOXO factors take over to determine the fate of a cell, long-term survival in a quiescent state, or programmed cell death. This review summarizes our current understanding of the mechanisms by which PKB/Akt and FOXO factors regulate these decisions.
Key Words: apoptosis • cell cycle • oxidative stress • cytokines
This article has been cited by other articles:
|
|
 |
|
  Y. Behl, M. Siqueira, J. Ortiz, J. Li, T. Desta, D. Faibish, and D. T. Graves Activation of the Acquired Immune Response Reduces Coupled Bone Formation in Response to a Periodontal Pathogen J. Immunol., December 15, 2008; 181(12): 8711 - 8718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Gao, T. Tang, T. Guo, A. Miyanohara, T. Yajima, K. Pestonjamasp, J. R. Feramisco, and H. K. Hammond Adenylyl Cyclase Type VI Increases Akt Activity and Phospholamban Phosphorylation in Cardiac Myocytes J. Biol. Chem., November 28, 2008; 283(48): 33527 - 33535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Brenkman, P. L.J. de Keizer, N. J.F. van den Broek, P. van der Groep, P. J. van Diest, A. van der Horst, A. M.M. Smits, and B. M.T. Burgering The Peptidyl-Isomerase Pin1 Regulates p27kip1 Expression through Inhibition of Forkhead Box O Tumor Suppressors Cancer Res., September 15, 2008; 68(18): 7597 - 7605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. J. Frew, A. Minola, S. Georgiev, M. Hitz, H. Moch, S. Richard, A. O. Vortmeyer, and W. Krek Combined Vhlh and Pten Mutation Causes Genital Tract Cystadenoma and Squamous Metaplasia Mol. Cell. Biol., July 15, 2008; 28(14): 4536 - 4548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-M. Maira, F. Stauffer, J. Brueggen, P. Furet, C. Schnell, C. Fritsch, S. Brachmann, P. Chene, A. De Pover, K. Schoemaker, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity Mol. Cancer Ther., July 1, 2008; 7(7): 1851 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakamura, H. Sakaue, A. Nishizawa, Y. Matsuki, H. Gomi, E. Watanabe, R. Hiramatsua, M. Tamamori-Adachi, S. Kitajima, T. Noda, et al. PDK1 Regulates Cell Proliferation and Cell Cycle Progression through Control of Cyclin D1 and p27Kip1 Expression J. Biol. Chem., June 20, 2008; 283(25): 17702 - 17711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hoogeboom, M. A. G. Essers, P. E. Polderman, E. Voets, L. M. M. Smits, and B. M. Th. Burgering Interaction of FOXO with {beta}-Catenin Inhibits {beta}-Catenin/T Cell Factor Activity J. Biol. Chem., April 4, 2008; 283(14): 9224 - 9230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Pardo, M. A. Lopez, and A. M. Boriek FOXO transcription factors are mechanosensitive and their regulation is altered with aging in the respiratory pump Am J Physiol Cell Physiol, April 1, 2008; 294(4): C1056 - C1066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Chiribau, L. Cheng, I. C. Cucoranu, Y.-S. Yu, R. E. Clempus, and D. Sorescu FOXO3A Regulates Peroxiredoxin III Expression in Human Cardiac Fibroblasts J. Biol. Chem., March 28, 2008; 283(13): 8211 - 8217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cui, Y. Huang, Y. Zhao, and J. Zheng Transcription Factor FOXO3a Mediates Apoptosis in HIV-1-Infected Macrophages J. Immunol., January 15, 2008; 180(2): 898 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ekoff, T. Kaufmann, M. Engstrom, N. Motoyama, A. Villunger, J.-I. Jonsson, A. Strasser, and G. Nilsson The BH3-only protein Puma plays an essential role in cytokine deprivation induced apoptosis of mast cells Blood, November 1, 2007; 110(9): 3209 - 3217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Doucet, A. P. Russell, B. Leger, R. Debigare, D. R. Joanisse, M.-A. Caron, P. LeBlanc, and F. Maltais Muscle Atrophy and Hypertrophy Signaling in Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., August 1, 2007; 176(3): 261 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Batista, D. Vaiman, J. Dausset, M. Fellous, and R. A. Veitia Potential targets of FOXL2, a transcription factor involved in craniofacial and follicular development, identified by transcriptomics PNAS, February 27, 2007; 104(9): 3330 - 3335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Hinman, J. N. Bushanam, W. A. Nichols, and A. B. Satterthwaite B Cell Receptor Signaling Down-Regulates Forkhead Box Transcription Factor Class O 1 mRNA Expression via Phosphatidylinositol 3-Kinase and Bruton's Tyrosine Kinase J. Immunol., January 15, 2007; 178(2): 740 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Bogoyevitch and B. Kobe Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases Microbiol. Mol. Biol. Rev., December 1, 2006; 70(4): 1061 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Dupont-Versteegden, B. A. Strotman, C. M. Gurley, D. Gaddy, M. Knox, J. D. Fluckey, and C. A. Peterson Nuclear translocation of EndoG at the initiation of disuse muscle atrophy and apoptosis is specific to myonuclei Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1730 - R1740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Ellsworth, N. Egashira, J. L. Haller, D. L. Butts, J. Cocquet, C. M. Clay, R. Y. Osamura, and S. A. Camper FOXL2 in the Pituitary: Molecular, Genetic, and Developmental Analysis Mol. Endocrinol., November 1, 2006; 20(11): 2796 - 2805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Leger, R. Cartoni, M. Praz, S. Lamon, O. Deriaz, A. Crettenand, C. Gobelet, P. Rohmer, M. Konzelmann, F. Luthi, et al. Akt signalling through GSK-3{beta}, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy J. Physiol., November 1, 2006; 576(3): 923 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Gude, J. Muraski, M. Rubio, J. Kajstura, E. Schaefer, P. Anversa, and M. A. Sussman Akt Promotes Increased Cardiomyocyte Cycling and Expansion of the Cardiac Progenitor Cell Population Circ. Res., August 18, 2006; 99(4): 381 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Huang, N. Erdmann, H. Peng, S. Herek, J. S. Davis, X. Luo, T. Ikezu, and J. Zheng TRAIL-Mediated Apoptosis in HIV-1-Infected Macrophages Is Dependent on the Inhibition of Akt-1 Phosphorylation J. Immunol., August 15, 2006; 177(4): 2304 - 2313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Reagan-Shaw and N. Ahmad RNA Interference-Mediated Depletion of Phosphoinositide 3-Kinase Activates Forkhead Box Class O Transcription Factors and Induces Cell Cycle Arrest and Apoptosis in Breast Carcinoma Cells Cancer Res., January 15, 2006; 66(2): 1062 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Boiko, S. Porteous, O. V. Razorenova, V. I. Krivokrysenko, B. R. Williams, and A. V. Gudkov A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation Genes & Dev., January 15, 2006; 20(2): 236 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Liu, S. Wang, S. Wei, L. Sun, and X. Feng Receptor Activator of NF-{kappa}B (RANK) Cytoplasmic Motif, 369PFQEP373, Plays a Predominant Role in Osteoclast Survival in Part by Activating Akt/PKB and Its Downstream Effector AFX/FOXO4 J. Biol. Chem., December 30, 2005; 280(52): 43064 - 43072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Wu, M. B. Zelinski, D. K. Ingram, and M. A. Ottinger Ovarian Aging and Menopause: Current Theories, Hypotheses, and Research Models Experimental Biology and Medicine, December 1, 2005; 230(11): 818 - 828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Perrot and M. M. Rechler The Coactivator p300 Directly Acetylates the Forkhead Transcription Factor Foxo1 and Stimulates Foxo1-Induced Transcription Mol. Endocrinol., September 1, 2005; 19(9): 2283 - 2298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fu, C. Wang, M. Rao, X. Wu, T. Bouras, X. Zhang, Z. Li, X. Jiao, J. Yang, A. Li, et al. Cyclin D1 Represses p300 Transactivation through a Cyclin-dependent Kinase-independent Mechanism J. Biol. Chem., August 19, 2005; 280(33): 29728 - 29742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Luo, C. L. Sobkiw, N. M. Logsdon, J. M. Watt, S. Signoretti, F. O'Connell, E. Shin, Y. Shim, L. Pao, B. G. Neel, et al. Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide 3-kinase PNAS, July 19, 2005; 102(29): 10238 - 10243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Machida, H. Inoue, K. Matsumoto, M. Tsuda, S. Fukuyama, H. Koto, H. Aizawa, Y. Kureishi, N. Hara, and Y. Nakanishi Activation of PI3K-Akt pathway mediates antiapoptotic effects of {beta}-adrenergic agonist in airway eosinophils Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L860 - L867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alikhani, Z. Alikhani, and D. T. Graves FOXO1 Functions as a Master Switch That Regulates Gene Expression Necessary for Tumor Necrosis Factor-induced Fibroblast Apoptosis J. Biol. Chem., April 1, 2005; 280(13): 12096 - 12102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Park, E. T. Maizels, Z. J. Feiger, H. Alam, C. A. Peters, T. K. Woodruff, T. G. Unterman, E. J. Lee, J. L. Jameson, and M. Hunzicker-Dunn Induction of Cyclin D2 in Rat Granulosa Cells Requires FSH-dependent Relief from FOXO1 Repression Coupled with Positive Signals from Smad J. Biol. Chem., March 11, 2005; 280(10): 9135 - 9148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jiang, S. E. Moriarty-Craige, M. Orr, J. Cai, P. Sternberg Jr, and D. P. Jones Oxidant-Induced Apoptosis in Human Retinal Pigment Epithelial Cells: Dependence on Extracellular Redox State Invest. Ophthalmol. Vis. Sci., March 1, 2005; 46(3): 1054 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. McCormick, Y. Feng, K. Dawson, M. J. Behne, B. Yu, J. Wang, A. W. Wyatt, G. Henke, F. Grahammer, T. M. Mauro, et al. Targeted Disruption of the Protein Kinase SGK3/CISK Impairs Postnatal Hair Follicle Development Mol. Biol. Cell, September 1, 2004; 15(9): 4278 - 4288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Spaner Amplifying cancer vaccine responses by modifying pathogenic gene programs in tumor cells J. Leukoc. Biol., August 1, 2004; 76(2): 338 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Cunningham, Q. Zhu, and J. M. Hammond FoxO1a Can Alter Cell Cycle Progression by Regulating the Nuclear Localization of p27kip in Granulosa Cells Mol. Endocrinol., July 1, 2004; 18(7): 1756 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Bommhardt, K. C. Chang, P. E. Swanson, T. H. Wagner, K. W. Tinsley, I. E. Karl, and R. S. Hotchkiss Akt Decreases Lymphocyte Apoptosis and Improves Survival in Sepsis J. Immunol., June 15, 2004; 172(12): 7583 - 7591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cooray The pivotal role of phosphatidylinositol 3-kinase-Akt signal transduction in virus survival J. Gen. Virol., May 1, 2004; 85(5): 1065 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Daly, V. Wong, E. Burova, Y. Wei, S. Zabski, J. Griffiths, K.-M. Lai, H. C. Lin, E. Ioffe, G. D. Yancopoulos, et al. Angiopoietin-1 modulates endothelial cell function and gene expression via the transcription factor FKHR (FOXO1) Genes & Dev., May 1, 2004; 18(9): 1060 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hosaka, W. H. Biggs III, D. Tieu, A. D. Boyer, N. M. Varki, W. K. Cavenee, and K. C. Arden Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification PNAS, March 2, 2004; 101(9): 2975 - 2980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. B. Dansen, G. J. P. L. Kops, S. Denis, N. Jelluma, R. J. A. Wanders, J. L. Bos, B. M. T. Burgering, and K. W. A. Wirtz Regulation of sterol carrier protein gene expression by the Forkhead transcription factor FOXO3a J. Lipid Res., January 1, 2004; 45(1): 81 - 88. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
