Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 295 (5564): 2450-2452

Copyright © 2002 by the American Association for the Advancement of Science

Redox Regulation of Forkhead Proteins Through a p66shc-Dependent Signaling Pathway

Shino Nemoto, Toren Finkel*

Genetic determinants of longevity include the forkhead-related transcription factor DAF-16 in the worm Caenorhabditis elegans and the p66shc locus in mice. We demonstrate that p66shc regulates intracellular oxidant levels in mammalian cells and that hydrogen peroxide can negatively regulate forkhead activity. In p66shc-/- cells, the activity of the mammalian forkhead homolog FKHRL1 is increased and redox-dependent forkhead inactivation is reduced. In addition, expression of FKHRL1 results in an increase in both hydrogen peroxide scavenging and oxidative stress resistance. These results demonstrate an important functional relation between three distinct elements linked to aging: forkhead proteins, p66shc, and intracellular oxidants.

Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10/6N-240, 10 Center Drive, Bethesda, MD 20892-1622, USA.
*   To whom correspondence should be addressed. E-mail: finkelt{at}

Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling.
N. Alic, T. D. Andrews, M. E. Giannakou, I. Papatheodorou, C. Slack, M. P. Hoddinott, H. M. Cocheme, E. F. Schuster, J. M. Thornton, and L. Partridge (2014)
Mol Syst Biol 7, 502
   Abstract »    Full Text »    PDF »
SirT3 Regulates the Mitochondrial Unfolded Protein Response.
L. Papa and D. Germain (2014)
Mol. Cell. Biol. 34, 699-710
   Abstract »    Full Text »    PDF »
Intra-renal transfection of heat shock protein 90 alpha or beta (Hsp90{alpha} or Hsp90{beta}) protects against ischemia/reperfusion injury.
J. Barrera-Chimal, R. Perez-Villalva, J. A. Ortega, N. Uribe, G. Gamba, C. Cortes-Gonzalez, and N. A. Bobadilla (2014)
Nephrol. Dial. Transplant. 29, 301-312
   Abstract »    Full Text »    PDF »
FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells.
H. Yeo, C. A. Lyssiotis, Y. Zhang, H. Ying, J. M. Asara, L. C. Cantley, and J.-H. Paik (2013)
EMBO J. 32, 2589-2602
   Abstract »    Full Text »    PDF »
Interference with Akt Signaling Protects Against Myocardial Infarction and Death by Limiting the Consequences of Oxidative Stress.
B. A. Kerr, L. Ma, X. Z. West, L. Ding, N. L. Malinin, M. E. Weber, M. Tischenko, A. Goc, P. R. Somanath, M. S. Penn, et al. (2013)
Science Signaling 6, ra67
   Abstract »    Full Text »    PDF »
Arginase-II Induces Vascular Smooth Muscle Cell Senescence and Apoptosis Through p66Shc and p53 Independently of Its l-Arginine Ureahydrolase Activity: Implications for Atherosclerotic Plaque Vulnerability.
Y. Xiong, Y. Yu, J.-P. Montani, Z. Yang, and X.-F. Ming (2013)
JAHA 2, e000096
   Abstract »    Full Text »    PDF »
Oxidative stress response elicited by mitochondrial dysfunction: Implication in the pathophysiology of aging.
C.-H. Wang, S.-B. Wu, Y.-T. Wu, and Y.-H. Wei (2013)
Experimental Biology and Medicine 238, 450-460
   Abstract »    Full Text »    PDF »
Type 5 Adenylyl Cyclase Increases Oxidative Stress by Transcriptional Regulation of Manganese Superoxide Dismutase via the SIRT1/FoxO3a Pathway.
L. Lai, L. Yan, S. Gao, C.-L. Hu, H. Ge, A. Davidow, M. Park, C. Bravo, K. Iwatsubo, Y. Ishikawa, et al. (2013)
Circulation 127, 1692-1701
   Abstract »    Full Text »    PDF »
Transcription Factor Foxo3a Prevents Apoptosis by Regulating Calcium through the Apoptosis Repressor with Caspase Recruitment Domain.
D. Lu, J. Liu, J. Jiao, B. Long, Q. Li, W. Tan, and P. Li (2013)
J. Biol. Chem. 288, 8491-8504
   Abstract »    Full Text »    PDF »
Loss of TIMP3 underlies diabetic nephropathy via FoxO1/STAT1 interplay.
L. Fiorentino, M. Cavalera, S. Menini, V. Marchetti, M. Mavilio, M. Fabrizi, F. Conserva, V. Casagrande, R. Menghini, P. Pontrelli, et al. (2013)
EMBO Mol Med. 5, 441-455
   Abstract »    Full Text »    PDF »
FOXO Transcription Factors Regulate Innate Immune Mechanisms in Respiratory Epithelial Cells.
F. Seiler, J. Hellberg, P. M. Lepper, A. Kamyschnikow, C. Herr, M. Bischoff, F. Langer, H.-J. Schafers, F. Lammert, M. D. Menger, et al. (2013)
J. Immunol. 190, 1603-1613
   Abstract »    Full Text »    PDF »
Suppression of Oxidative Stress by {beta}-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor.
T. Shimazu, M. D. Hirschey, J. Newman, W. He, K. Shirakawa, N. Le Moan, C. A. Grueter, H. Lim, L. R. Saunders, R. D. Stevens, et al. (2013)
Science 339, 211-214
   Abstract »    Full Text »    PDF »
Impaired myogenesis in estrogen-related receptor {gamma} (ERR{gamma})-deficient skeletal myocytes due to oxidative stress.
J. Murray, J. Auwerx, and J. M. Huss (2013)
FASEB J 27, 135-150
   Abstract »    Full Text »    PDF »
Null mutations at the p66 and bradykinin 2 receptor loci induce divergent phenotypes in the diabetic kidney.
H. Vashistha, P. C. Singhal, A. Malhotra, M. Husain, P. Mathieson, M. A. Saleem, C. Kuriakose, S. Seshan, A. Wilk, L. DelValle, et al. (2012)
Am J Physiol Renal Physiol 303, F1629-F1640
   Abstract »    Full Text »    PDF »
S1P1 expression is controlled by the pro-oxidant activity of p66Shc and is impaired in B-CLL patients with unfavorable prognosis.
N. Capitani, L. Patrussi, L. Trentin, O. M. Lucherini, E. Cannizzaro, E. Migliaccio, F. Frezzato, C. Gattazzo, F. Forconi, P. Pelicci, et al. (2012)
Blood 120, 4391-4399
   Abstract »    Full Text »    PDF »
Diverging Antioxidative Responses to IGF-1 in Cultured Human Skin Fibroblasts Versus Vascular Endothelial Cells.
R. C. Stone, S. Kim, B. J. Barnes, and A. Aviv (2012)
J Gerontol A Biol Sci Med Sci 67, 939-946
   Abstract »    Full Text »    PDF »
Involvement of the Up-regulated FoxO1 Expression in Follicular Granulosa Cell Apoptosis Induced by Oxidative Stress.
M. Shen, F. Lin, J. Zhang, Y. Tang, W.-K. Chen, and H. Liu (2012)
J. Biol. Chem. 287, 25727-25740
   Abstract »    Full Text »    PDF »
Insulin-Like Growth Factors and Insulin: At the Crossroad Between Tumor Development and Longevity.
R. Novosyadlyy and D. LeRoith (2012)
J Gerontol A Biol Sci Med Sci 67A, 640-651
   Abstract »    Full Text »    PDF »
MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival.
N. T. Nehme, J. P. Schmid, F. Debeurme, I. Andre-Schmutz, A. Lim, P. Nitschke, F. Rieux-Laucat, P. Lutz, C. Picard, N. Mahlaoui, et al. (2012)
Blood 119, 3458-3468
   Abstract »    Full Text »    PDF »
FoxO1 as a double-edged sword in the pancreas: analysis of pancreas- and {beta}-cell-specific FoxO1 knockout mice.
M. Kobayashi, O. Kikuchi, T. Sasaki, H.-J. Kim, H. Yokota-Hashimoto, Y.-S. Lee, K. Amano, T. Kitazumi, V. Y. Susanti, Y. I. Kitamura, et al. (2012)
Am J Physiol Endocrinol Metab 302, E603-E613
   Abstract »    Full Text »    PDF »
FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption.
I. V. Nechipurenko and H. T. Broihier (2012)
J. Cell Biol. 196, 345-362
   Abstract »    Full Text »    PDF »
Novel role of p66Shc in ROS-dependent VEGF signaling and angiogenesis in endothelial cells.
J. Oshikawa, S.-J. Kim, E. Furuta, C. Caliceti, G.-F. Chen, R. D. McKinney, F. Kuhr, I. Levitan, T. Fukai, and M. Ushio-Fukai (2012)
Am J Physiol Heart Circ Physiol 302, H724-H732
   Abstract »    Full Text »    PDF »
Oxidative stress in the haematopoietic niche regulates the cellular immune response in Drosophila.
S. A. Sinenko, J. Shim, and U. Banerjee (2012)
EMBO Rep. 13, 83-89
   Abstract »    Full Text »    PDF »
HIV gene expression deactivates redox-sensitive stress response program in mouse tubular cells both in vitro and in vivo.
D. Salhan, S. Pathak, M. Husain, P. Tandon, D. Kumar, A. Malhotra, L. G. Meggs, and P. C. Singhal (2012)
Am J Physiol Renal Physiol 302, F129-F140
   Abstract »    Full Text »    PDF »
Applications of post-translational modifications of FoxO family proteins in biological functions.
Y. Zhao, Y. Wang, and W.-G. Zhu (2011)
J Mol Cell Biol 3, 276-282
   Abstract »    Full Text »    PDF »
Repression of P66Shc Expression by SIRT1 Contributes to the Prevention of Hyperglycemia-Induced Endothelial Dysfunction.
S. Zhou, H.-Z. Chen, Y.-z. Wan, Q.-J. Zhang, Y.-S. Wei, S. Huang, J.-J. Liu, Y.-B. Lu, Z.-Q. Zhang, R.-F. Yang, et al. (2011)
Circ. Res. 109, 639-648
   Abstract »    Full Text »    PDF »
Oxidized Low-Density Lipoprotein Activates p66Shc via Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1, Protein Kinase C-{beta}, and c-Jun N-Terminal Kinase Kinase in Human Endothelial Cells.
Y. Shi, F. Cosentino, G. G. Camici, A. Akhmedov, P. M. Vanhoutte, F. C. Tanner, and T. F. Luscher (2011)
Arterioscler Thromb Vasc Biol 31, 2090-2097
   Abstract »    Full Text »    PDF »
FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3.
J. Araujo, P. Breuer, S. Dieringer, S. Krauss, S. Dorn, K. Zimmermann, A. Pfeifer, T. Klockgether, U. Wuellner, and B. O. Evert (2011)
Hum. Mol. Genet. 20, 2928-2941
   Abstract »    Full Text »    PDF »
Apurinic/apyrimidinic endonuclease 1 inhibits protein kinase C-mediated p66shc phosphorylation and vasoconstriction.
S. K. Lee, J. I. Chung, M. S. Park, H. K. Joo, E. J. Lee, E. J. Cho, J. B. Park, S. Ryoo, K. Irani, and B. H. Jeon (2011)
Cardiovasc Res 91, 502-509
   Abstract »    Full Text »    PDF »
Signal transduction by reactive oxygen species.
T. Finkel (2011)
J. Cell Biol. 194, 7-15
   Abstract »    Full Text »    PDF »
Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor.
E. Gonzalez, E. Flier, D. Molle, D. Accili, and T. E. McGraw (2011)
PNAS 108, 10162-10167
   Abstract »    Full Text »    PDF »
Osteoclast Response to Low Extracellular Sodium and the Mechanism of Hyponatremia-induced Bone Loss.
J. Barsony, Y. Sugimura, and J. G. Verbalis (2011)
J. Biol. Chem. 286, 10864-10875
   Abstract »    Full Text »    PDF »
Titanium Topography Controls FoxO/{beta}-catenin Signaling.
C. Galli, G. M. Macaluso, M. Piemontese, and G. Passeri (2011)
Journal of Dental Research 90, 360-364
   Abstract »    PDF »
Cancer Cell Metabolism.
R. A. Cairns, I. Harris, S. McCracken, and T. W. Mak (2011)
Cold Spring Harb Symp Quant Biol 76, 299-311
   Abstract »    Full Text »    PDF »
p53 Impairs Endothelial Function by Transcriptionally Repressing Kruppel-Like Factor 2.
A. Kumar, C.-S. Kim, T. A. Hoffman, A. Naqvi, J. DeRicco, S.-B. Jung, Z. Lin, M. K. Jain, and K. Irani (2011)
Arterioscler Thromb Vasc Biol 31, 133-141
   Abstract »    Full Text »    PDF »
ROS-mediated amplification of AKT/mTOR signalling pathway leads to myeloproliferative syndrome in Foxo3-/- mice.
S. Yalcin, D. Marinkovic, S. K. Mungamuri, X. Zhang, W. Tong, R. Sellers, and S. Ghaffari (2010)
EMBO J. 29, 4118-4131
   Abstract »    Full Text »    PDF »
Wnt Signaling and Aging-Related Heart Disorders.
A. T. Naito, I. Shiojima, and I. Komuro (2010)
Circ. Res. 107, 1295-1303
   Abstract »    Full Text »    PDF »
The Forkhead Transcription Factor Hcm1 Promotes Mitochondrial Biogenesis and Stress Resistance in Yeast.
M. J. Rodriguez-Colman, G. Reverter-Branchat, M. A. Sorolla, J. Tamarit, J. Ros, and E. Cabiscol (2010)
J. Biol. Chem. 285, 37092-37101
   Abstract »    Full Text »    PDF »
Activation of Forkhead Box O Transcription Factors by Oncogenic BRAF Promotes p21cip1-Dependent Senescence.
P. L. J. de Keizer, L. M. Packer, A. A. Szypowska, P. E. Riedl-Polderman, N. J. F. van den Broek, A. de Bruin, T. B. Dansen, R. Marais, A. B. Brenkman, and B. M. T. Burgering (2010)
Cancer Res. 70, 8526-8536
   Abstract »    Full Text »    PDF »
Elevated expression of protein kinase C{delta} induces cell scattering upon serum deprivation.
C.-L. Chen, P.-C. Chan, S.-H. Wang, Y.-R. Pan, and H.-C. Chen (2010)
J. Cell Sci. 123, 2901-2913
   Abstract »    Full Text »    PDF »
Uncoupling of Acetylation from Phosphorylation Regulates FoxO1 Function Independent of Its Subcellular Localization.
L. Qiang, A. S. Banks, and D. Accili (2010)
J. Biol. Chem. 285, 27396-27401
   Abstract »    Full Text »    PDF »
miR-451 protects against erythroid oxidant stress by repressing 14-3-3{zeta}.
D. Yu, C. O. dos Santos, G. Zhao, J. Jiang, J. D. Amigo, E. Khandros, L. C. Dore, Y. Yao, J. D'Souza, Z. Zhang, et al. (2010)
Genes & Dev. 24, 1620-1633
   Abstract »    Full Text »    PDF »
The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis.
S. Perrini, L. Laviola, M. C. Carreira, A. Cignarelli, A. Natalicchio, and F. Giorgino (2010)
J. Endocrinol. 205, 201-210
   Abstract »    Full Text »    PDF »
p66Shc Is Indispensable for Phenethyl Isothiocyanate-Induced Apoptosis in Human Prostate Cancer Cells.
D. Xiao and S. V. Singh (2010)
Cancer Res. 70, 3150-3158
   Abstract »    Full Text »    PDF »
A NADPH Oxidase-Dependent Redox Signaling Pathway Mediates the Selective Radiosensitization Effect of Parthenolide in Prostate Cancer Cells.
Y. Sun, D. K. St. Clair, Y. Xu, P. A. Crooks, and W. H. St. Clair (2010)
Cancer Res. 70, 2880-2890
   Abstract »    Full Text »    PDF »
Oxidative stress-specific interaction between FANCD2 and FOXO3a.
J. Li, W. Du, S. Maynard, P. R. Andreassen, and Q. Pang (2010)
Blood 115, 1545-1548
   Abstract »    Full Text »    PDF »
Restoration of p53 Functions Protects Cells from Concanavalin A-Induced Apoptosis.
A.R.M. R. Amin, V. S. Thakur, K. Gupta, M. W. Jackson, H. Harada, M. K. Agarwal, D. M. Shin, D. N. Wald, and M. L. Agarwal (2010)
Mol. Cancer Ther. 9, 471-479
   Abstract »    Full Text »    PDF »
Regulation of the Intracellular Localization of Foxo3a by Stress-Activated Protein Kinase Signaling Pathways in Skeletal Muscle Cells.
S. Clavel, S. Siffroi-Fernandez, A. S. Coldefy, K. Boulukos, D. F. Pisani, and B. Derijard (2010)
Mol. Cell. Biol. 30, 470-480
   Abstract »    Full Text »    PDF »
Transcriptional repression of Kruppel like factor-2 by the adaptor protein p66shc.
A. Kumar, T. A. Hoffman, J. DeRicco, A. Naqvi, M. K. Jain, and K. Irani (2009)
FASEB J 23, 4344-4352
   Abstract »    Full Text »    PDF »
FoxM1, a critical regulator of oxidative stress during oncogenesis.
H. J. Park, J. R. Carr, Z. Wang, V. Nogueira, N. Hay, A. L. Tyner, L. F. Lau, R. H. Costa, and P. Raychaudhuri (2009)
EMBO J. 28, 2908-2918
   Abstract »    Full Text »    PDF »
FOXO3a Promotes Tumor Cell Invasion through the Induction of Matrix Metalloproteinases.
P. Storz, H. Doppler, J. A. Copland, K. J. Simpson, and A. Toker (2009)
Mol. Cell. Biol. 29, 4906-4917
   Abstract »    Full Text »    PDF »
Long-Lived Ames Dwarf Mice Are Resistant to Chemical Stressors.
A. F. Bokov, M. L. Lindsey, C. Khodr, M. R. Sabia, and A. Richardson (2009)
J Gerontol A Biol Sci Med Sci 64A, 819-827
   Abstract »    Full Text »    PDF »
FOXO3a Is Broadly Neuroprotective In Vitro and In Vivo against Insults Implicated in Motor Neuron Diseases.
J. Mojsilovic-Petrovic, N. Nedelsky, M. Boccitto, I. Mano, S. N. Georgiades, W. Zhou, Y. Liu, R. L. Neve, J. P. Taylor, M. Driscoll, et al. (2009)
J. Neurosci. 29, 8236-8247
   Abstract »    Full Text »    PDF »
Inhibition of p66ShcA Longevity Gene Rescues Podocytes from HIV-1-induced Oxidative Stress and Apoptosis.
M. Husain, L. G. Meggs, H. Vashistha, S. Simoes, K. O. Griffiths, D. Kumar, J. Mikulak, P. W. Mathieson, M. A. Saleem, L. Del Valle, et al. (2009)
J. Biol. Chem. 284, 16648-16658
   Abstract »    Full Text »    PDF »
Mutual Dependence of Foxo3a and PGC-1{alpha} in the Induction of Oxidative Stress Genes.
Y. Olmos, I. Valle, S. Borniquel, A. Tierrez, E. Soria, S. Lamas, and M. Monsalve (2009)
J. Biol. Chem. 284, 14476-14484
   Abstract »    Full Text »    PDF »
Mirk/Dyrk1B Maintains the Viability of Quiescent Pancreatic Cancer Cells by Reducing Levels of Reactive Oxygen Species.
X. Deng, D. Z. Ewton, and E. Friedman (2009)
Cancer Res. 69, 3317-3324
   Abstract »    Full Text »    PDF »
FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation.
Y. Mei, Y. Zhang, K. Yamamoto, W. Xie, T. W. Mak, and H. You (2009)
PNAS 106, 5153-5158
   Abstract »    Full Text »    PDF »
p66Shc Links {alpha}1-Adrenergic Receptors to a Reactive Oxygen Species-Dependent AKT-FOXO3A Phosphorylation Pathway in Cardiomyocytes.
J. Guo, Z. Gertsberg, N. Ozgen, and S. F. Steinberg (2009)
Circ. Res. 104, 660-669
   Abstract »    Full Text »    PDF »
Positive and negative feedback regulates the transcription factor FOXL2 in response to cell stress: evidence for a regulatory imbalance induced by disease-causing mutations.
B. A. Benayoun, F. Batista, J. Auer, A. Dipietromaria, D. L'Hote, E. De Baere, and R. A. Veitia (2009)
Hum. Mol. Genet. 18, 632-644
   Abstract »    Full Text »    PDF »
p66Shc-generated Oxidative Signal Promotes Fat Accumulation.
I. Berniakovich, M. Trinei, M. Stendardo, E. Migliaccio, S. Minucci, P. Bernardi, P. G. Pelicci, and M. Giorgio (2008)
J. Biol. Chem. 283, 34283-34293
   Abstract »    Full Text »    PDF »
P53 Impairs Endothelium-Dependent Vasomotor Function Through Transcriptional Upregulation of P66shc.
C.-S. Kim, S.-B. Jung, A. Naqvi, T. A. Hoffman, J. DeRicco, T. Yamamori, M. P. Cole, B.-H. Jeon, and K. Irani (2008)
Circ. Res. 103, 1441-1450
   Abstract »    Full Text »    PDF »
Abnormalities of IGF-I signaling in the pathogenesis of diseases of the bone, brain, and fetoplacental unit in humans.
L. Laviola, A. Natalicchio, S. Perrini, and F. Giorgino (2008)
Am J Physiol Endocrinol Metab 295, E991-E999
   Abstract »    Full Text »    PDF »
Foxo3 Is Essential for the Regulation of Ataxia Telangiectasia Mutated and Oxidative Stress-mediated Homeostasis of Hematopoietic Stem Cells.
S. Yalcin, X. Zhang, J. P. Luciano, S. K. Mungamuri, D. Marinkovic, C. Vercherat, A. Sarkar, M. Grisotto, R. Taneja, and S. Ghaffari (2008)
J. Biol. Chem. 283, 25692-25705
   Abstract »    Full Text »    PDF »
Permanent embryo arrest: molecular and cellular concepts.
D.H. Betts and P. Madan (2008)
Mol. Hum. Reprod. 14, 445-453
   Abstract »    Full Text »    PDF »
Endothelin-1 Couples {beta}Pix to p66Shc: Role of {beta}Pix in Cell Proliferation through FOXO3a Phosphorylation and p27kip1 Down-Regulation Independently of Akt.
A. Chahdi and A. Sorokin (2008)
Mol. Biol. Cell 19, 2609-2619
   Abstract »    Full Text »    PDF »
The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of lymphocyte activation and autoimmunity.
F. Finetti, M. Pellegrini, C. Ulivieri, M. T. Savino, E. Paccagnini, C. Ginanneschi, L. Lanfrancone, P. G. Pelicci, and C. T. Baldari (2008)
Blood 111, 5017-5027
   Abstract »    Full Text »    PDF »
Transforming signals resulting from sustained activation of the PDGF{beta} receptor in mortal human fibroblasts.
L. M. Petti, E. C. Ricciardi, H. J. Page, and K. A. Porter (2008)
J. Cell Sci. 121, 1172-1182
   Abstract »    Full Text »    PDF »
FOXO3A Regulates Peroxiredoxin III Expression in Human Cardiac Fibroblasts.
C. B. Chiribau, L. Cheng, I. C. Cucoranu, Y.-S. Yu, R. E. Clempus, and D. Sorescu (2008)
J. Biol. Chem. 283, 8211-8217
   Abstract »    Full Text »    PDF »
Forkhead Factor, FOXO3a, Induces Apoptosis of Endothelial Cells Through Activation of Matrix Metalloproteinases.
H.-Y. Lee, H.-J. You, J.-Y. Won, S.-W. Youn, H.-J. Cho, K.-W. Park, W.-Y. Park, J.-S. Seo, Y.-B. Park, K. Walsh, et al. (2008)
Arterioscler Thromb Vasc Biol 28, 302-308
   Abstract »    Full Text »    PDF »
Transcription Factor FOXO3a Mediates Apoptosis in HIV-1-Infected Macrophages.
M. Cui, Y. Huang, Y. Zhao, and J. Zheng (2008)
J. Immunol. 180, 898-906
   Abstract »    Full Text »    PDF »
Forkhead Transcription Factors and Cardiovascular Biology.
K. N. Papanicolaou, Y. Izumiya, and K. Walsh (2008)
Circ. Res. 102, 16-31
   Abstract »    Full Text »    PDF »
FOXO3a Turns the Tumor Necrosis Factor Receptor Signaling Towards Apoptosis Through Reciprocal Regulation of c-Jun N-Terminal Kinase and NF-{kappa}B.
H.-Y. Lee, S.-W. Youn, J.-Y. Kim, K.-W. Park, C.-I. Hwang, W.-Y. Park, B.-H. Oh, Y.-B. Park, K. Walsh, J.-S. Seo, et al. (2008)
Arterioscler Thromb Vasc Biol 28, 112-120
   Abstract »    Full Text »    PDF »
AGE-receptor-1 counteracts cellular oxidant stress induced by AGEs via negative regulation of p66shc-dependent FKHRL1 phosphorylation.
W. Cai, J. C. He, L. Zhu, X. Chen, G. E. Striker, and H. Vlassara (2008)
Am J Physiol Cell Physiol 294, C145-C152
   Abstract »    Full Text »    PDF »
Chronological and replicative life-span extension in Saccharomyces cerevisiae by increased dosage of alcohol dehydrogenase 1.
G. Reverter-Branchat, E. Cabiscol, J. Tamarit, M. A. Sorolla, M. Angeles de la Torre, and J. Ros (2007)
Microbiology 153, 3667-3676
   Abstract »    Full Text »    PDF »
Oxidative Stress Antagonizes Wnt Signaling in Osteoblast Precursors by Diverting beta-Catenin from T Cell Factor- to Forkhead Box O-mediated Transcription.
M. Almeida, L. Han, M. Martin-Millan, C. A. O'Brien, and S. C. Manolagas (2007)
J. Biol. Chem. 282, 27298-27305
   Abstract »    Full Text »    PDF »
Dynamic FoxO transcription factors.
H. Huang and D. J. Tindall (2007)
J. Cell Sci. 120, 2479-2487
   Abstract »    Full Text »    PDF »
Role of FoxO1 in FFA-induced oxidative stress in adipocytes.
A. R. Subauste and C. F. Burant (2007)
Am J Physiol Endocrinol Metab 293, E159-E164
   Abstract »    Full Text »    PDF »
FOXO Transcription Factors in the Regulatory Networks of Longevity.
H. Daitoku and A. Fukamizu (2007)
J. Biochem. 141, 769-774
   Abstract »    Full Text »    PDF »
The emerging role of FOXO transcription factors in pancreatic {beta} cells.
D. A Glauser and W. Schlegel (2007)
J. Endocrinol. 193, 195-207
   Abstract »    Full Text »    PDF »
Genetic deletion of p66Shc adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress.
G. G. Camici, M. Schiavoni, P. Francia, M. Bachschmid, I. Martin-Padura, M. Hersberger, F. C. Tanner, P. Pelicci, M. Volpe, P. Anversa, et al. (2007)
PNAS 104, 5217-5222
   Abstract »    Full Text »    PDF »
Mitochondrial Dysfunction in Atherosclerosis.
N. R. Madamanchi and M. S. Runge (2007)
Circ. Res. 100, 460-473
   Abstract »    Full Text »    PDF »
Inhibition of wild-type p66ShcA in mesangial cells prevents glycooxidant-dependent FOXO3a regulation and promotes the survival phenotype.
J. Chintapalli, S. Yang, D. Opawumi, S. R. Goyal, N. Shamsuddin, A. Malhotra, K. Reiss, and L. G. Meggs (2007)
Am J Physiol Renal Physiol 292, F523-F530
   Abstract »    Full Text »    PDF »
Critical Role for FoxO3a-Dependent Regulation of p21CIP1/WAF1 in Response to Statin Signaling in Cardiac Myocytes.
L. Hauck, C. Harms, D. Grothe, J. An, K. Gertz, G. Kronenberg, R. Dietz, M. Endres, and R. von Harsdorf (2007)
Circ. Res. 100, 50-60
   Abstract »    Full Text »    PDF »
An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations.
K. C. Kregel and H. J. Zhang (2007)
Am J Physiol Regulatory Integrative Comp Physiol 292, R18-R36
   Abstract »    Full Text »    PDF »
A Novel Class of Vascular Endothelial Growth Factor-responsive Genes That Require Forkhead Activity for Expression.
Md. R. Abid, S.-C. Shih, H. H. Otu, K. C. Spokes, Y. Okada, D. T. Curiel, T. Minami, and W. C. Aird (2006)
J. Biol. Chem. 281, 35544-35553
   Abstract »    Full Text »    PDF »
Oxidant-mediated Akt Activation in Human RPE Cells..
P. Yang, J. J. Peairs, R. Tano, and G. J. Jaffe (2006)
Invest. Ophthalmol. Vis. Sci. 47, 4598-4606
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 3-Kinase-dependent Suppression of the Human Inducible Nitric-oxide Synthase Promoter Is Mediated by FKHRL1.
A. S. Kristof, J. Fielhaber, A. Triantafillopoulos, S. Nemoto, and J. Moss (2006)
J. Biol. Chem. 281, 23958-23968
   Abstract »    Full Text »    PDF »
Distinct Signaling Functions for Shc Isoforms in the Heart.
M. Obreztchikova, H. Elouardighi, M. Ho, B. A. Wilson, Z. Gertsberg, and S. F. Steinberg (2006)
J. Biol. Chem. 281, 20197-20204
   Abstract »    Full Text »    PDF »
Atrogin-1/MAFbx and MuRF1 Are Downregulated in Aging-Related Loss of Skeletal Muscle.
E. Edstrom, M. Altun, M. Hagglund, and B. Ulfhake (2006)
J Gerontol A Biol Sci Med Sci 61, 663-674
   Abstract »    Full Text »    PDF »
Regulation of transactivation-independent proapoptotic activity of p53 by FOXO3a.
H. You, K. Yamamoto, and T. W. Mak (2006)
PNAS 103, 9051-9056
   Abstract »    Full Text »    PDF »
The Mammalian Longevity-associated Gene Product p66shc Regulates Mitochondrial Metabolism.
S. Nemoto, C. A. Combs, S. French, B.-H. Ahn, M. M. Fergusson, R. S. Balaban, and T. Finkel (2006)
J. Biol. Chem. 281, 10555-10560
   Abstract »    Full Text »    PDF »
Inhibition of LINE-1 expression in the heart decreases ischemic damage by activation of Akt/PKB signaling.
E. Lucchinetti, J. Feng, R. d. Silva, G. V. Tolstonog, M. C. Schaub, G. G. Schumann, and M. Zaugg (2006)
Physiol Genomics 25, 314-324
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882