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.

Originally published in Science Express on 7 March 2002
Science 29 March 2002:
Vol. 295. no. 5564, pp. 2450 - 2452
DOI: 10.1126/science.1069004
Prev | Table of Contents | Next

Reports

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}nih.gov

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Protection against Loss of Innate Defenses in Adulthood by Low Advanced Glycation End Products (AGE) Intake: Role of the Antiinflammatory AGE Receptor-1.
H. Vlassara, W. Cai, S. Goodman, R. Pyzik, A. Yong, X. Chen, L. Zhu, T. Neade, M. Beeri, J. M. Silverman, et al. (2009)
J. Clin. Endocrinol. Metab. 94, 4483-4491
   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 »
p66shc Negatively Regulates Insulin-Like Growth Factor I Signal Transduction via Inhibition of p52shc Binding to Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate-1 Leading to Impaired Growth Factor Receptor-Bound Protein-2 Membrane Recruitment.
G. Xi, X. Shen, and D. R. Clemmons (2008)
Mol. Endocrinol. 22, 2162-2175
   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 »
Oral Glycotoxins Determine the Effects of Calorie Restriction on Oxidant Stress, Age-Related Diseases, and Lifespan.
W. Cai, J. C. He, L. Zhu, X. Chen, F. Zheng, G. E. Striker, and H. Vlassara (2008)
Am. J. Pathol. 173, 327-336
   Abstract »    Full Text »    PDF »
Oxidative Stress Stimulates Testicular Orphan Receptor 4 through Forkhead Transcription Factor Forkhead Box O3a.
G. Li, Y.-F. Lee, S. Liu, Y. Cai, S. Xie, N.-C. Liu, B.-Y. Bao, Z. Chen, and C. Chang (2008)
Endocrinology 149, 3490-3499
   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 »
Gone with the Wnts: {beta}-Catenin, T-Cell Factor, Forkhead Box O, and Oxidative Stress in Age-Dependent Diseases of Bone, Lipid, and Glucose Metabolism.
S. C. Manolagas and M. Almeida (2007)
Mol. Endocrinol. 21, 2605-2614
   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 »
Reduced Oxidant Stress and Extended Lifespan in Mice Exposed to a Low Glycotoxin Diet: Association with Increased AGER1 Expression.
W. Cai, J. C. He, L. Zhu, X. Chen, S. Wallenstein, G. E. Striker, and H. Vlassara (2007)
Am. J. Pathol. 170, 1893-1902
   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 »
Differential Expression of FOXO1 and FOXO3a Confers Resistance to Oxidative Cell Death upon Endometrial Decidualization.
T. Kajihara, M. Jones, L. Fusi, M. Takano, F. Feroze-Zaidi, G. Pirianov, H. Mehmet, O. Ishihara, J. M. Higham, E. W.-F. Lam, et al. (2006)
Mol. Endocrinol. 20, 2444-2455
   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 »
Sos-mediated activation of rac1 by p66shc.
F. A. Khanday, L. Santhanam, K. Kasuno, T. Yamamori, A. Naqvi, J. DeRicco, A. Bugayenko, I. Mattagajasingh, A. Disanza, G. Scita, et al. (2006)
J. Cell Biol. 172, 817-822
   Abstract »    Full Text »    PDF »
RUNX3 Cooperates with FoxO3a to Induce Apoptosis in Gastric Cancer Cells.
Y. Yamamura, W. L. Lee, K.-i. Inoue, H. Ida, and Y. Ito (2006)
J. Biol. Chem. 281, 5267-5276
   Abstract »    Full Text »    PDF »
p53 Mediates the Accelerated Onset of Senescence of Endothelial Progenitor Cells in Diabetes.
A. Rosso, A. Balsamo, R. Gambino, P. Dentelli, R. Falcioni, M. Cassader, L. Pegoraro, G. Pagano, and M. F. Brizzi (2006)
J. Biol. Chem. 281, 4339-4347
   Abstract »    Full Text »    PDF »
Accelerated Ovarian Failure Induced by 4-Vinyl Cyclohexene Diepoxide in Nrf2 Null Mice.
X. Hu, J. R. Roberts, P. L. Apopa, Y. W. Kan, and Q. Ma (2006)
Mol. Cell. Biol. 26, 940-954
   Abstract »    Full Text »    PDF »
Genetics of aging: implications for drug discovery and development.
B. J Geesaman (2006)
Am. J. Clinical Nutrition 83, 466S-469S
   Abstract »    Full Text »    PDF »
Rac1 Leads to Phosphorylation-dependent Increase in Stability of the p66shc Adaptor Protein: Role in Rac1-induced Oxidative Stress.
F. A. Khanday, T. Yamamori, I. Mattagajasingh, Z. Zhang, A. Bugayenko, A. Naqvi, L. Santhanam, N. Nabi, K. Kasuno, B. W. Day, et al. (2006)
Mol. Biol. Cell 17, 122-129
   Abstract »    Full Text »    PDF »
Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1 in Caloric Restriction and Other Models of Longevity.
J. C. Corton and H. M. Brown-Borg (2005)
J. Gerontol. A Biol. Sci. Med. Sci. 60, 1494-1509
   Abstract »    Full Text »    PDF »
Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice.
X. Liu, N. Jiang, B. Hughes, E. Bigras, E. Shoubridge, and S. Hekimi (2005)
Genes & Dev. 19, 2424-2434
   Abstract »    Full Text »    PDF »
Protein Kinase D Mediates Mitochondrion-to-Nucleus Signaling and Detoxification from Mitochondrial Reactive Oxygen Species.
P. Storz, H. Doppler, and A. Toker (2005)
Mol. Cell. Biol. 25, 8520-8530
   Abstract »    Full Text »    PDF »
Redox Regulation of PTEN by S-Nitrosothiols.
C.-X. Yu, S. Li, and A. R. Whorton (2005)
Mol. Pharmacol. 68, 847-854
   Abstract »    Full Text »    PDF »
ERK Phosphorylates p66shcA on Ser36 and Subsequently Regulates p27kip1 Expression via the Akt-FOXO3a Pathway: Implication of p27kip1 in Cell Response to Oxidative Stress.
Y. Hu, X. Wang, L. Zeng, D.-Y. Cai, K. Sabapathy, S. P. Goff, E. J. Firpo, and B. Li (2005)
Mol. Biol. Cell 16, 3705-3718
   Abstract »    Full Text »    PDF »
Glucose-dependent Insulinotropic Polypeptide (GIP) Stimulation of Pancreatic {beta}-Cell Survival Is Dependent upon Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (PKB) Signaling, Inactivation of the Forkhead Transcription Factor Foxo1, and Down-regulation of bax Expression.
S.-J. Kim, K. Winter, C. Nian, M. Tsuneoka, Y. Koda, and C. H. S. McIntosh (2005)
J. Biol. Chem. 280, 22297-22307
   Abstract »    Full Text »    PDF »
Nuclear Trapping of the Forkhead Transcription Factor FoxO1 via Sirt-dependent Deacetylation Promotes Expression of Glucogenetic Genes.
D. Frescas, L. Valenti, and D. Accili (2005)
J. Biol. Chem. 280, 20589-20595
   Abstract »    Full Text »    PDF »
Phosphorylation of p66Shc and forkhead proteins mediates A{beta} toxicity.
W. W. Smith, D. D. Norton, M. Gorospe, H. Jiang, S. Nemoto, N. J. Holbrook, T. Finkel, and J. W. Kusiak (2005)
J. Cell Biol. 169, 331-339
   Abstract »    Full Text »    PDF »
SIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1{alpha}.
S. Nemoto, M. M. Fergusson, and T. Finkel (2005)
J. Biol. Chem. 280, 16456-16460
   Abstract »    Full Text »    PDF »
S-Nitrosylation-dependent Inactivation of Akt/Protein Kinase B in Insulin Resistance.
T. Yasukawa, E. Tokunaga, H. Ota, H. Sugita, J. A. J. Martyn, and M. Kaneki (2005)
J. Biol. Chem. 280, 7511-7518
   Abstract »    Full Text »    PDF »
Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen species.
J. H. Kim, S. C. Chu, J. L. Gramlich, Y. B. Pride, E. Babendreier, D. Chauhan, R. Salgia, K. Podar, J. D. Griffin, and M. Sattler (2005)
Blood 105, 1717-1723
   Abstract »    Full Text »    PDF »
Down-Regulation of a Forkhead Transcription Factor, FOXO3a, Accelerates Cellular Senescence in Human Dermal Fibroblasts.
H. Kyoung Kim, Y. Kyoung Kim, I.-H. Song, S.-H. Baek, S.-R. Lee, J. Hye Kim, and J.-R. Kim (2005)
J. Gerontol. A Biol. Sci. Med. Sci. 60, 4-9
   Abstract »    Full Text »    PDF »
Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress.
M. Shapira, E. Segal, and D. Botstein (2004)
Mol. Biol. Cell 15, 5659-5669
   Abstract »    Full Text »    PDF »
MUC1 Oncoprotein Activates the FOXO3a Transcription Factor in a Survival Response to Oxidative Stress.
L. Yin, L. Huang, and D. Kufe (2004)
J. Biol. Chem. 279, 45721-45727
   Abstract »    Full Text »    PDF »
Role of the p66Shc Isoform in Insulin-like Growth Factor I Receptor Signaling through MEK/Erk and Regulation of Actin Cytoskeleton in Rat Myoblasts.
A. Natalicchio, L. Laviola, C. De Tullio, L. A. Renna, C. Montrone, S. Perrini, G. Valenti, G. Procino, M. Svelto, and F. Giorgino (2004)
J. Biol. Chem. 279, 43900-43909
   Abstract »    Full Text »    PDF »
p53-dependent inhibition of FKHRL1 in response to DNA damage through protein kinase SGK1.
H. You, Y. Jang, A. I. You-Ten, H. Okada, J. Liepa, A. Wakeham, K. Zaugg, and T. W. Mak (2004)
PNAS 101, 14057-14062
   Abstract »    Full Text »    PDF »
Abnormal Angiogenesis in Foxo1 (Fkhr)-deficient Mice.
T. Furuyama, K. Kitayama, Y. Shimoda, M. Ogawa, K. Sone, K. Yoshida-Araki, H. Hisatsune, S.-i. Nishikawa, K. Nakayama, K. Nakayama, et al. (2004)
J. Biol. Chem. 279, 34741-34749
   Abstract »    Full Text »    PDF »
Ticking Fast or Ticking Slow, Through Shc Must You Go?.
F. M. Martin and J. S. Friedman (2004)
Sci. Aging Knowl. Environ. 2004, pe32
   Abstract »    Full Text »
Murine Models of Life Span Extension.
J. K. Quarrie and K. T. Riabowol (2004)
Sci. Aging Knowl. Environ. 2004, re5
   Abstract »    Full Text »    PDF »
Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity.
H. Daitoku, M. Hatta, H. Matsuzaki, S. Aratani, T. Ohshima, M. Miyagishi, T. Nakajima, and A. Fukamizu (2004)
PNAS 101, 10042-10047
   Abstract »    Full Text »    PDF »
Contribution of caveolin-1{alpha} and Akt to TNF-{alpha}-induced cell death.
K. Ono, Y. Iwanaga, M. Hirayama, T. Kawamura, N. Sowa, and K. Hasegawa (2004)
Am J Physiol Lung Cell Mol Physiol 287, L201-L209
   Abstract »    Full Text »    PDF »
p66ShcA Modulates Tissue Response to Hindlimb Ischemia.
G. Zaccagnini, F. Martelli, P. Fasanaro, A. Magenta, C. Gaetano, A. Di Carlo, P. Biglioli, M. Giorgio, I. Martin-Padura, P. G. Pelicci, et al. (2004)
Circulation 109, 2917-2923
   Abstract »    Full Text »    PDF »
The Life Span Determinant p66Shc Localizes to Mitochondria Where It Associates with Mitochondrial Heat Shock Protein 70 and Regulates Trans-membrane Potential.
F. Orsini, E. Migliaccio, M. Moroni, C. Contursi, V. A. Raker, D. Piccini, I. Martin-Padura, G. Pelliccia, M. Trinei, M. Bono, et al. (2004)
J. Biol. Chem. 279, 25689-25695
   Abstract »    Full Text »    PDF »
Peroxiredoxin-null Yeast Cells Are Hypersensitive to Oxidative Stress and Are Genomically Unstable.
C.-M. Wong, K.-L. Siu, and D.-Y. Jin (2004)
J. Biol. Chem. 279, 23207-23213
   Abstract »    Full Text »    PDF »
Androgens Negatively Regulate Forkhead Transcription Factor FKHR (FOXO1) through a Proteolytic Mechanism in Prostate Cancer Cells.
H. Huang, D. C. Muddiman, and D. J. Tindall (2004)
J. Biol. Chem. 279, 13866-13877
   Abstract »    Full Text »    PDF »
Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase.
A. Brunet, L. B. Sweeney, J. F. Sturgill, K. F. Chua, P. L. Greer, Y. Lin, H. Tran, S. E. Ross, R. Mostoslavsky, H. Y. Cohen, et al. (2004)
Science 303, 2011-2015
   Abstract »    Full Text »    PDF »
p66SHC Promotes Apoptosis and Antagonizes Mitogenic Signaling in T Cells.
S. Pacini, M. Pellegrini, E. Migliaccio, L. Patrussi, C. Ulivieri, A. Ventura, F. Carraro, A. Naldini, L. Lanfrancone, P. Pelicci, et al. (2004)
Mol. Cell. Biol. 24, 1747-1757
   Abstract »    Full Text »    PDF »
The Akt-regulated Forkhead Transcription Factor FOXO3a Controls Endothelial Cell Viability through Modulation of the Caspase-8 Inhibitor FLIP.
C. Skurk, H. Maatz, H.-S. Kim, J. Yang, M. R. Abid, W. C. Aird, and K. Walsh (2004)
J. Biol. Chem. 279, 1513-1525
   Abstract »    Full Text »    PDF »
Regulation of sterol carrier protein gene expression by the Forkhead transcription factor FOXO3a.
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 (2004)
J. Lipid Res. 45, 81-88
   Abstract »    Full Text »    PDF »
Shc Proteins Are Strong, Independent Prognostic Markers for Both Node-Negative and Node-Positive Primary Breast Cancer.
P. A. Davol, R. Bagdasaryan, G. J. Elfenbein, A. L. Maizel, and A. R. Frackelton Jr. (2003)
Cancer Res. 63, 6772-6783
   Abstract »    Full Text »    PDF »
Neutrophil activation by fMLP regulates FOXO (forkhead) transcription factors by multiple pathways, one of which includes the binding of FOXO to the survival factor Mcl-1.
L. J. Crossley (2003)
J. Leukoc. Biol. 74, 583-592
   Abstract »    Full Text »    PDF »
Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation.
H. Matsuzaki, H. Daitoku, M. Hatta, K. Tanaka, and A. Fukamizu (2003)
PNAS 100, 11285-11290
   Abstract »    Full Text »    PDF »
Human MUC1 Carcinoma Antigen Regulates Intracellular Oxidant Levels and the Apoptotic Response to Oxidative Stress.
L. Yin, Y. Li, J. Ren, H. Kuwahara, and D. Kufe (2003)
J. Biol. Chem. 278, 35458-35464
   Abstract »    Full Text »    PDF »
Alterations of gene expression in failing myocardium following left ventricular assist device support.
Y. Chen, S. Park, Y. Li, E. Missov, M. Hou, X. Han, J. L. Hall, L. W. Miller, and R. J. Bache (2003)
Physiol Genomics 14, 251-260
   Abstract »    Full Text »    PDF »
Characterization of Insulin Inhibition of Transactivation by a C-terminal Fragment of the Forkhead Transcription Factor Foxo1 in Rat Hepatoma Cells.
V. Perrot and M. M. Rechler (2003)
J. Biol. Chem. 278, 26111-26119
   Abstract »    Full Text »    PDF »
Gab1 Is an Integrator of Cell Death versus Cell Survival Signals in Oxidative Stress.
M. Holgado-Madruga and A. J. Wong (2003)
Mol. Cell. Biol. 23, 4471-4484
   Abstract »    Full Text »    PDF »
Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB/Akt is off duty.
B. M. T. Burgering and R. H. Medema (2003)
J. Leukoc. Biol. 73, 689-701
   Abstract »    Full Text »    PDF »
Caveolin-Induced Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Increases Arsenite Cytotoxicity.
S. Shack, X.-T. Wang, G. C. Kokkonen, M. Gorospe, D. L. Longo, and N. J. Holbrook (2003)
Mol. Cell. Biol. 23, 2407-2414
   Abstract »    Full Text »    PDF »
The Many Forks in FOXO's Road.
H. Tran, A. Brunet, E. C. Griffith, and M. E. Greenberg (2003)
Sci. STKE 2003, re5
   Abstract »    Full Text »    PDF »
p66Shc-/- Mice (Shc1tm1Pgp Mice).
(2003)
Sci. Aging Knowl. Environ. 2003, tg4-4
   Full Text »
Redox signaling in the growth and development of colonial hydroids.
N. W. Blackstone (2003)
J. Exp. Biol. 206, 651-658
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)