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 300 (5625): 1574-1577

Copyright © 2003 by the American Association for the Advancement of Science

TRB3: A tribbles Homolog That Inhibits Akt/PKB Activation by Insulin in Liver

Keyong Du,1* Stephan Herzig,1* Rohit N. Kulkarni,2 Marc Montminy1{dagger}

Abstract: Insulin resistance is a major hallmark in the development of type II diabetes, which is characterized by the failure of insulin to promote glucose uptake in muscle and to suppress glucose production in liver. The serine-threonine kinase Akt (PKB) is a principal target of insulin signaling that inhibits hepatic glucose output when glucose is available from food. Here we show that TRB3, a mammalian homolog of Drosophila tribbles, functions as a negative modulator of Akt. TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase. Amounts of TRB3 RNA and protein were increased in livers of db/db diabetic mice compared with those in wild-type mice. Hepatic overexpression of TRB3 in amounts comparable to those in db/db mice promoted hyperglycemia and glucose intolerance. Our results suggest that, by interfering with Akt activation, TRB3 contributes to insulin resistance in individuals with susceptibility to type II diabetes.

1 Peptide Biology Laboratories, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037—1002, USA.
2 Joslin Diabetes Center, Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.

Back to Top

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: montminy{at}

TRIB1 downregulates hepatic lipogenesis and glycogenesis via multiple molecular interactions.
Y. Ishizuka, K. Nakayama, A. Ogawa, S. Makishima, S. Boonvisut, A. Hirao, Y. Iwasaki, T. Yada, Y. Yanagisawa, H. Miyashita, et al. (2014)
J. Mol. Endocrinol. 52, 145-158
   Abstract »    Full Text »    PDF »
Tribbles Homolog 3 Attenuates Mammalian Target of Rapamycin Complex-2 Signaling and Inflammation in the Diabetic Kidney.
E. Borsting, S. V. Patel, A.-E. Decleves, S. J. Lee, Q. M. Rahman, S. Akira, J. Satriano, K. Sharma, V. Vallon, and R. Cunard (2014)
J. Am. Soc. Nephrol.
   Abstract »
Peroxisome Proliferator-Activated Receptor {delta} Agonist GW1516 Attenuates Diet-Induced Aortic Inflammation, Insulin Resistance, and Atherosclerosis in Low-Density Lipoprotein Receptor Knockout Mice.
L. A. Bojic, A. C. Burke, S. S. Chhoker, D. E. Telford, B. G. Sutherland, J. Y. Edwards, C. G. Sawyez, R. G. Tirona, H. Yin, J. G. Pickering, et al. (2014)
Arterioscler Thromb Vasc Biol 34, 52-60
   Abstract »    Full Text »    PDF »
Acceleration of Biliary Cholesterol Secretion Restores Glycemic Control and Alleviates Hypertriglyceridemia in Obese db/db Mice.
K. Su, N. S. Sabeva, Y. Wang, X. Liu, J. D. Lester, J. Liu, S. Liang, and G. A. Graf (2014)
Arterioscler Thromb Vasc Biol 34, 26-33
   Abstract »    Full Text »    PDF »
Insulin Receptor Signaling in Normal and Insulin-Resistant States.
J. Boucher, A. Kleinridders, and C. R. Kahn (2014)
Cold Spring Harb Perspect Biol 6, a009191
   Abstract »    Full Text »    PDF »
TRIB3 Mediates Glucose-Induced Insulin Resistance via a Mechanism That Requires the Hexosamine Biosynthetic Pathway.
W. Zhang, J. Liu, L. Tian, Q. Liu, Y. Fu, and W. T. Garvey (2013)
Diabetes 62, 4192-4200
   Abstract »    Full Text »    PDF »
DHHC17 Palmitoylates ClipR-59 and Modulates ClipR-59 Association with the Plasma Membrane.
W. Ren, Y. Sun, and K. Du (2013)
Mol. Cell. Biol. 33, 4255-4265
   Abstract »    Full Text »    PDF »
Role of Fas-Associated Death Domain-containing Protein (FADD) Phosphorylation in Regulating Glucose Homeostasis: from Proteomic Discovery to Physiological Validation.
C. Yao, H. Zhuang, P. Du, W. Cheng, B. Yang, S. Guan, Y. Hu, D. Zhu, M. Christine, L. Shi, et al. (2013)
Mol. Cell. Proteomics 12, 2689-2700
   Abstract »    Full Text »    PDF »
Candidate Tumor Suppressor and pVHL Partner Jade-1 Binds and Inhibits AKT in Renal Cell Carcinoma.
L. Zeng, M. Bai, A. K. Mittal, W. El-Jouni, J. Zhou, D. M. Cohen, M. I. Zhou, and H. T. Cohen (2013)
Cancer Res. 73, 5371-5380
   Abstract »    Full Text »    PDF »
Upregulation of CHOP/GADD153 during Coronavirus Infectious Bronchitis Virus Infection Modulates Apoptosis by Restricting Activation of the Extracellular Signal-Regulated Kinase Pathway.
Y. Liao, T. S. Fung, M. Huang, S. G. Fang, Y. Zhong, and D. X. Liu (2013)
J. Virol. 87, 8124-8134
   Abstract »    Full Text »    PDF »
High Mobility Group N Proteins Modulate the Fidelity of the Cellular Transcriptional Profile in a Tissue- and Variant-specific Manner.
J. E. Kugler, M. Horsch, D. Huang, T. Furusawa, M. Rochman, L. Garrett, L. Becker, A. Bohla, S. M. Holter, C. Prehn, et al. (2013)
J. Biol. Chem. 288, 16690-16703
   Abstract »    Full Text »    PDF »
Insulin relaxes bladder via PI3K/AKT/eNOS pathway activation in mucosa: unfolded protein response-dependent insulin resistance as a cause of obesity-associated overactive bladder.
L. O. Leiria, C. Sollon, F. R. Bau, F. Z. Monica, C. L. D'Ancona, G. De Nucci, A. D. Grant, G. F. Anhe, and E. Antunes (2013)
J. Physiol. 591, 2259-2273
   Abstract »    Full Text »    PDF »
Interaction of Constitutive Photomorphogenesis 1 Protein with Protein-Tyrosine Phosphatase 1B Suppresses Protein-Tyrosine Phosphatase 1B Activity and Enhances Insulin Signaling.
W. Ren, Y. Sun, S. Cheema, and K. Du (2013)
J. Biol. Chem. 288, 10902-10913
   Abstract »    Full Text »    PDF »
High throughput kinase inhibitor screens reveal TRB3 and MAPK-ERK/TGF{beta} pathways as fundamental Notch regulators in breast cancer.
J. Izrailit, H. K. Berman, A. Datti, J. L. Wrana, and M. Reedijk (2013)
PNAS 110, 1714-1719
   Abstract »    Full Text »    PDF »
Lysine 63-linked Ubiquitination Modulates Mixed Lineage Kinase-3 Interaction with JIP1 Scaffold Protein in Cytokine-induced Pancreatic {beta} Cell Death.
R. K. Humphrey, S. M. A. Yu, A. Bellary, S. Gonuguntla, M. Yebra, and U. S. Jhala (2013)
J. Biol. Chem. 288, 2428-2440
   Abstract »    Full Text »    PDF »
Greater insulin-mediated Akt phosphorylation concomitant with heterogeneous effects on phosphorylation of Akt substrates in soleus of calorie-restricted rats.
N. Sharma, D. A. Sequea, E. B. Arias, and G. D. Cartee (2012)
Am J Physiol Regulatory Integrative Comp Physiol 303, R1261-R1267
   Abstract »    Full Text »    PDF »
Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice.
H. Li, M. Xu, J. Lee, C. He, and Z. Xie (2012)
Am J Physiol Endocrinol Metab 303, E1234-E1244
   Abstract »    Full Text »    PDF »
Human Tribbles 3 Protects Nuclear DNA from Cytidine Deamination by APOBEC3A.
M.-M. Aynaud, R. Suspene, P.-O. Vidalain, B. Mussil, D. Guetard, F. Tangy, S. Wain-Hobson, and J.-P. Vartanian (2012)
J. Biol. Chem. 287, 39182-39192
   Abstract »    Full Text »    PDF »
Systematic Analysis of Protein Phosphorylation Networks From Phosphoproteomic Data.
C. Song, M. Ye, Z. Liu, H. Cheng, X. Jiang, G. Han, Z. Songyang, Y. Tan, H. Wang, J. Ren, et al. (2012)
Mol. Cell. Proteomics 11, 1070-1083
   Abstract »    Full Text »    PDF »
Role of TRIB3 in regulation of insulin sensitivity and nutrient metabolism during short-term fasting and nutrient excess.
J. Liu, W. Zhang, G. C. Chuang, H. S. Hill, L. Tian, Y. Fu, D. R. Moellering, and W. T. Garvey (2012)
Am J Physiol Endocrinol Metab 303, E908-E916
   Abstract »    Full Text »    PDF »
The ABCG5 ABCG8 Sterol Transporter Opposes the Development of Fatty Liver Disease and Loss of Glycemic Control Independently of Phytosterol Accumulation.
K. Su, N. S. Sabeva, J. Liu, Y. Wang, S. Bhatnagar, D. R. van der Westhuyzen, and G. A. Graf (2012)
J. Biol. Chem. 287, 28564-28575
   Abstract »    Full Text »    PDF »
The Association of ClipR-59 Protein with AS160 Modulates AS160 Protein Phosphorylation and Adipocyte Glut4 Protein Membrane Translocation.
W. Ren, S. Cheema, and K. Du (2012)
J. Biol. Chem. 287, 26890-26900
   Abstract »    Full Text »    PDF »
Dual functions of adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1 (APPL1) in insulin signaling and insulin secretion.
W. Han (2012)
PNAS 109, 8795-8796
   Full Text »    PDF »
Role of TRIB3 in Diabetic and Overnutrition-Induced Atherosclerosis.
J. R. Sowers (2012)
Diabetes 61, 265-266
   Full Text »    PDF »
Silence of TRIB3 Suppresses Atherosclerosis and Stabilizes Plaques in Diabetic ApoE-/-/LDL Receptor-/- Mice.
Z.-h. Wang, Y.-y. Shang, S. Zhang, M. Zhong, X.-p. Wang, J.-t. Deng, J. Pan, Y. Zhang, and W. Zhang (2012)
Diabetes 61, 463-473
   Abstract »    Full Text »    PDF »
Carbohydrate Metabolism Is Perturbed in Peroxisome-deficient Hepatocytes Due to Mitochondrial Dysfunction, AMP-activated Protein Kinase (AMPK) Activation, and Peroxisome Proliferator-activated Receptor {gamma} Coactivator 1{alpha} (PGC-1{alpha}) Suppression.
A. Peeters, P. Fraisl, S. van den Berg, E. Ver Loren van Themaat, A. Van Kampen, M. H. Rider, H. Takemori, K. W. van Dijk, P. P. Van Veldhoven, P. Carmeliet, et al. (2011)
J. Biol. Chem. 286, 42162-42179
   Abstract »    Full Text »    PDF »
APPL1 Counteracts Obesity-Induced Vascular Insulin Resistance and Endothelial Dysfunction by Modulating the Endothelial Production of Nitric Oxide and Endothelin-1 in Mice.
Y. Wang, K. K. Y. Cheng, K. S. L. Lam, D. Wu, Y. Wang, Y. Huang, P. M. Vanhoutte, G. Sweeney, Y. Li, and A. Xu (2011)
Diabetes 60, 3044-3054
   Abstract »    Full Text »    PDF »
TRB3 Gene Silencing Alleviates Diabetic Cardiomyopathy in a Type 2 Diabetic Rat Model.
Y. Ti, G.-l. Xie, Z.-h. Wang, X.-l. Bi, W.-y. Ding, J. Wang, G.-h. Jiang, P.-l. Bu, Y. Zhang, M. Zhong, et al. (2011)
Diabetes 60, 2963-2974
   Abstract »    Full Text »    PDF »
TRB3 interacts with SMAD3 promoting tumor cell migration and invasion.
F. Hua, R. Mu, J. Liu, J. Xue, Z. Wang, H. Lin, H. Yang, X. Chen, and Z. Hu (2011)
J. Cell Sci. 124, 3235-3246
   Abstract »    Full Text »    PDF »
Histone Deacetylase 7 Regulates Cell Survival and TCR Signaling in CD4/CD8 Double-Positive Thymocytes.
H. G. Kasler, B. D. Young, D. Mottet, H. W. Lim, A. M. Collins, E. N. Olson, and E. Verdin (2011)
J. Immunol. 186, 4782-4793
   Abstract »    Full Text »    PDF »
Transformation by Tribbles homolog 2 (Trib2) requires both the Trib2 kinase domain and COP1 binding.
K. Keeshan, W. Bailis, P. H. Dedhia, M. E. Vega, O. Shestova, L. Xu, K. Toscano, S. N. Uljon, S. C. Blacklow, and W. S. Pear (2010)
Blood 116, 4948-4957
   Abstract »    Full Text »    PDF »
TRB3 is stimulated in diabetic kidneys, regulated by the ER stress marker CHOP, and is a suppressor of podocyte MCP-1.
E. Morse, J. Schroth, Y.-H. You, D. P. Pizzo, S. Okada, S. RamachandraRao, V. Vallon, K. Sharma, and R. Cunard (2010)
Am J Physiol Renal Physiol 299, F965-F972
   Abstract »    Full Text »    PDF »
TRB3: an oxidant stress-induced pseudokinase with a potential to negatively modulate MCP-1 cytokine in diabetic nephropathy.
Y. S. Kanwar (2010)
Am J Physiol Renal Physiol 299, F963-F964
   Full Text »    PDF »
Elevated hepatic fatty acid elongase-5 activity corrects dietary fat-induced hyperglycemia in obese BL/6J mice.
S. Tripathy, M. Torres-Gonzalez, and D. B. Jump (2010)
J. Lipid Res. 51, 2642-2654
   Abstract »    Full Text »    PDF »
Improvement of Retinal Vascular Injury in Diabetic Rats by Statins Is Associated With the Inhibition of Mitochondrial Reactive Oxygen Species Pathway Mediated by Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1{alpha}.
Z. Zheng, H. Chen, H. Wang, B. Ke, B. Zheng, Q. Li, P. Li, L. Su, Q. Gu, and X. Xu (2010)
Diabetes 59, 2315-2325
   Abstract »    Full Text »    PDF »
Differential ability of Tribbles family members to promote degradation of C/EBP{alpha} and induce acute myelogenous leukemia.
P. H. Dedhia, K. Keeshan, S. Uljon, L. Xu, M. E. Vega, O. Shestova, M. Zaks-Zilberman, C. Romany, S. C. Blacklow, and W. S. Pear (2010)
Blood 116, 1321-1328
   Abstract »    Full Text »    PDF »
UPR-mediated TRIB3 expression correlates with reduced AKT phosphorylation and inability of interleukin 6 to overcome palmitate-induced apoptosis in RINm5F cells.
J. E. Nicoletti-Carvalho, T. C. Araujo Nogueira, R. Gorjao, C. R. Bromati, T. S. Yamanaka, A. C. Boschero, L. A. Velloso, R. Curi, G. F. Anhe, and S. Bordin (2010)
J. Endocrinol. 206, 183-193
   Abstract »    Full Text »    PDF »
Control of Adipose Tissue Inflammation Through TRB1.
A. Ostertag, A. Jones, A. J. Rose, M. Liebert, S. Kleinsorg, A. Reimann, A. Vegiopoulos, M. B. Diaz, D. Strzoda, M. Yamamoto, et al. (2010)
Diabetes 59, 1991-2000
   Abstract »    Full Text »    PDF »
Mixed Lineage Kinase-3 Stabilizes and Functionally Cooperates with TRIBBLES-3 to Compromise Mitochondrial Integrity in Cytokine-induced Death of Pancreatic Beta Cells.
R. K. Humphrey, C. J. Newcomb, S.-M. A. Yu, E. Hao, D. Yu, S. Krajewski, K. Du, and U. S. Jhala (2010)
J. Biol. Chem. 285, 22426-22436
   Abstract »    Full Text »    PDF »
TRB3 Function in Cardiac Endoplasmic Reticulum Stress.
J. Avery, S. Etzion, B. J. DeBosch, X. Jin, T. S. Lupu, B. Beitinjaneh, J. Grand, A. Kovacs, N. Sambandam, and A. J. Muslin (2010)
Circ. Res. 106, 1516-1523
   Abstract »    Full Text »    PDF »
An integrative genomic approach in oesophageal cells identifies TRB3 as a bile acid responsive gene, downregulated in Barrett's oesophagus, which regulates NF-{kappa}B activation and cytokine levels.
S. P. Duggan, F. M. Behan, M. Kirca, S. Smith, J. V. Reynolds, A. Long, and D. Kelleher (2010)
Carcinogenesis 31, 936-945
   Abstract »    Full Text »    PDF »
Mammalian Tribbles homolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance.
J. Liu, X. Wu, J. L. Franklin, J. L. Messina, H. S. Hill, D. R. Moellering, R. G. Walton, M. Martin, and W. T. Garvey (2010)
Am J Physiol Endocrinol Metab 298, E565-E576
   Abstract »    Full Text »    PDF »
Regulation of mRNA translation in renal physiology and disease.
B. S. Kasinath, D. Feliers, K. Sataranatarajan, G. Ghosh Choudhury, M. J. Lee, and M. M. Mariappan (2009)
Am J Physiol Renal Physiol 297, F1153-F1165
   Abstract »    Full Text »    PDF »
E3 ubiquitin ligase COP1 regulates the stability and functions of MTA1.
D.-Q. Li, K. Ohshiro, S. D. N. Reddy, S. B. Pakala, M.-H. Lee, Y. Zhang, S. K. Rayala, and R. Kumar (2009)
PNAS 106, 17493-17498
   Abstract »    Full Text »    PDF »
Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes.
V. T. Samuel, S. A. Beddow, T. Iwasaki, X.-M. Zhang, X. Chu, C. D. Still, G. S. Gerhard, and G. I. Shulman (2009)
PNAS 106, 12121-12126
   Abstract »    Full Text »    PDF »
Activation and Signaling by the AMP-Activated Protein Kinase in Endothelial Cells.
B. Fisslthaler and I. Fleming (2009)
Circ. Res. 105, 114-127
   Abstract »    Full Text »    PDF »
The Small Molecule Phenamil Induces Osteoblast Differentiation and Mineralization.
K. W. Park, H. Waki, W.-K. Kim, B. S. J. Davies, S. G. Young, F. Parhami, and P. Tontonoz (2009)
Mol. Cell. Biol. 29, 3905-3914
   Abstract »    Full Text »    PDF »
TRIB3 Functional Q84R Polymorphism Is a Risk Factor for Metabolic Syndrome and Carotid Atherosclerosis.
H.-p. Gong, Z.-h. Wang, H. Jiang, N.-n. Fang, J.-s. Li, Y.-y. Shang, Y. Zhang, M. Zhong, and W. Zhang (2009)
Diabetes Care 32, 1311-1313
   Abstract »    Full Text »    PDF »
Palmitate Induces Insulin Resistance in H4IIEC3 Hepatocytes through Reactive Oxygen Species Produced by Mitochondria.
S. Nakamura, T. Takamura, N. Matsuzawa-Nagata, H. Takayama, H. Misu, H. Noda, S. Nabemoto, S. Kurita, T. Ota, H. Ando, et al. (2009)
J. Biol. Chem. 284, 14809-14818
   Abstract »    Full Text »    PDF »
Inactivation of hypothalamic FAS protects mice from diet-induced obesity and inflammation.
M. V. Chakravarthy, Y. Zhu, L. Yin, T. Coleman, K. L. Pappan, C. A. Marshall, M. L. McDaniel, and C. F. Semenkovich (2009)
J. Lipid Res. 50, 630-640
   Abstract »    Full Text »    PDF »
ClipR-59 Interacts with Akt and Regulates Akt Cellular Compartmentalization.
J. Ding and K. Du (2009)
Mol. Cell. Biol. 29, 1459-1471
   Abstract »    Full Text »    PDF »
Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species.
N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich (2009)
Physiol Rev 89, 27-71
   Abstract »    Full Text »    PDF »
COP1 Functions as a FoxO1 Ubiquitin E3 Ligase to Regulate FoxO1-mediated Gene Expression.
S. Kato, J. Ding, E. Pisck, U. S. Jhala, and K. Du (2008)
J. Biol. Chem. 283, 35464-35473
   Abstract »    Full Text »    PDF »
Paradoxical effects of increased expression of PGC-1{alpha} on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism.
C. S. Choi, D. E. Befroy, R. Codella, S. Kim, R. M. Reznick, Y.-J. Hwang, Z.-X. Liu, H.-Y. Lee, A. Distefano, V. T. Samuel, et al. (2008)
PNAS 105, 19926-19931
   Abstract »    Full Text »    PDF »
TRIB3 is implicated in glucotoxicity- and oestrogen receptor-stress-induced {beta}-cell apoptosis.
B. Qian, H. Wang, X. Men, W. Zhang, H. Cai, S. Xu, Y. Xu, L. Ye, C. B Wollheim, and J. Lou (2008)
J. Endocrinol. 199, 407-416
   Abstract »    Full Text »    PDF »
Tribbles-2 is a novel regulator of inflammatory activation of monocytes.
K. Eder, H. Guan, H. Y. Sung, J. Ward, A. Angyal, M. Janas, G. Sarmay, E. Duda, M. Turner, S. K. Dower, et al. (2008)
Int. Immunol. 20, 1543-1550
   Abstract »    Full Text »    PDF »
Double Tribble: Two TRIB3 Variants, Insulin, Akt, and eNOS.
I. Fleming (2008)
Arterioscler Thromb Vasc Biol 28, 1216-1218
   Full Text »    PDF »
TRIB3 R84 Variant Is Associated With Impaired Insulin-Mediated Nitric Oxide Production in Human Endothelial Cells.
F. Andreozzi, G. Formoso, S. Prudente, M. L. Hribal, A. Pandolfi, E. Bellacchio, S. Di Silvestre, V. Trischitta, A. Consoli, and G. Sesti (2008)
Arterioscler Thromb Vasc Biol 28, 1355-1360
   Abstract »    Full Text »    PDF »
Intracellular Signaling by Akt: Bound to Be Specific.
T. F. Franke (2008)
Science Signaling 1, pe29
   Abstract »    Full Text »    PDF »
Hepatic insulin resistance induced by prenatal alcohol exposure is associated with reduced PTEN and TRB3 acetylation in adult rat offspring.
X.-H. Yao and B. L. G. Nyomba (2008)
Am J Physiol Regulatory Integrative Comp Physiol 294, R1797-R1806
   Abstract »    Full Text »    PDF »
EPO receptor circuits for primary erythroblast survival.
P. Sathyanarayana, A. Dev, J. Fang, E. Houde, O. Bogacheva, O. Bogachev, M. Menon, S. Browne, A. Pradeep, C. Emerson, et al. (2008)
Blood 111, 5390-5399
   Abstract »    Full Text »    PDF »
TRB3 suppresses adipocyte differentiation by negatively regulating PPAR{gamma} transcriptional activity.
Y. Takahashi, N. Ohoka, H. Hayashi, and R. Sato (2008)
J. Lipid Res. 49, 880-892
   Abstract »    Full Text »    PDF »
Genetic Dissociation of Ethanol Sensitivity and Memory Formation in Drosophila melanogaster.
H. LaFerriere, D. J. Guarnieri, D. Sitaraman, S. Diegelmann, U. Heberlein, and T. Zars (2008)
Genetics 178, 1895-1902
   Abstract »    Full Text »    PDF »
Inhibition of Foxo1 Protects Pancreatic Islet {beta}-Cells Against Fatty Acid and Endoplasmic Reticulum Stress-Induced Apoptosis.
S. C. Martinez, K. Tanabe, C. Cras-Meneur, N. A. Abumrad, E. Bernal-Mizrachi, and M. A. Permutt (2008)
Diabetes 57, 846-859
   Abstract »    Full Text »    PDF »
Rapid Turnover of the mTOR Complex 1 (mTORC1) Repressor REDD1 and Activation of mTORC1 Signaling following Inhibition of Protein Synthesis.
S. R. Kimball, A. N. D. Do, L. Kutzler, D. R. Cavener, and L. S. Jefferson (2008)
J. Biol. Chem. 283, 3465-3475
   Abstract »    Full Text »    PDF »
Increasing {alpha}7{beta}1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression.
J. Liu, D. J. Burkin, and S. J. Kaufman (2008)
Am J Physiol Cell Physiol 294, C627-C640
   Abstract »    Full Text »    PDF »
Critical and Functional Regulation of CHOP (C/EBP Homologous Protein) through the N-terminal Portion.
N. Ohoka, T. Hattori, M. Kitagawa, K. Onozaki, and H. Hayashi (2007)
J. Biol. Chem. 282, 35687-35694
   Abstract »    Full Text »    PDF »
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
P. C. LaRosa, J.-J. M. Riethoven, H. Chen, Y. Xia, Y. Zhou, M. Chen, J. Miner, and M. E. Fromm (2007)
Physiol Genomics 31, 544-553
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress in the Heart.
C. C. Glembotski (2007)
Circ. Res. 101, 975-984
   Abstract »    Full Text »    PDF »
Carboxy-terminal modulator protein induces Akt phosphorylation and activation, thereby enhancing antiapoptotic, glycogen synthetic, and glucose uptake pathways.
H. Ono, H. Sakoda, M. Fujishiro, M. Anai, A. Kushiyama, Y. Fukushima, H. Katagiri, T. Ogihara, Y. Oka, H. Kamata, et al. (2007)
Am J Physiol Cell Physiol 293, C1576-C1585
   Abstract »    Full Text »    PDF »
TRB3 Blocks Adipocyte Differentiation through the Inhibition of C/EBP{beta} Transcriptional Activity.
O. Bezy, C. Vernochet, S. Gesta, S. R. Farmer, and C. R. Kahn (2007)
Mol. Cell. Biol. 27, 6818-6831
   Abstract »    Full Text »    PDF »
Selective progesterone receptor modulator asoprisnil induces endoplasmic reticulum stress in cultured human uterine leiomyoma cells.
Q. Xu, N. Ohara, J. Liu, K. Nakabayashi, D. DeManno, K. Chwalisz, S. Yoshida, and T. Maruo (2007)
Am J Physiol Endocrinol Metab 293, E1002-E1011
   Abstract »    Full Text »    PDF »
Enhanced TLR-mediated NF-IL6-dependent gene expression by Trib1 deficiency.
M. Yamamoto, S. Uematsu, T. Okamoto, Y. Matsuura, S. Sato, H. Kumar, T. Satoh, T. Saitoh, K. Takeda, K. J. Ishii, et al. (2007)
J. Exp. Med. 204, 2233-2239
   Abstract »    Full Text »    PDF »
Thematic review series: Adipocyte Biology. Adipocyte stress: the endoplasmic reticulum and metabolic disease.
M. F. Gregor and G. S. Hotamisligil (2007)
J. Lipid Res. 48, 1905-1914
   Abstract »    Full Text »    PDF »
Nelfinavir, A Lead HIV Protease Inhibitor, Is a Broad-Spectrum, Anticancer Agent that Induces Endoplasmic Reticulum Stress, Autophagy, and Apoptosis In vitro and In vivo.
J. J. Gills, J. LoPiccolo, J. Tsurutani, R. H. Shoemaker, C. J.M. Best, M. S. Abu-Asab, J. Borojerdi, N. A. Warfel, E. R. Gardner, M. Danish, et al. (2007)
Clin. Cancer Res. 13, 5183-5194
   Abstract »    Full Text »    PDF »
TRB2, a Mouse Tribbles Ortholog, Suppresses Adipocyte Differentiation by Inhibiting AKT and C/EBPbeta.
T. Naiki, E. Saijou, Y. Miyaoka, K. Sekine, and A. Miyajima (2007)
J. Biol. Chem. 282, 24075-24082
   Abstract »    Full Text »    PDF »
Protein-tyrosine Phosphatase 1B Deficiency Reduces Insulin Resistance and the Diabetic Phenotype in Mice with Polygenic Insulin Resistance.
B. Xue, Y.-B. Kim, A. Lee, E. Toschi, S. Bonner-Weir, C. R. Kahn, B. G. Neel, and B. B. Kahn (2007)
J. Biol. Chem. 282, 23829-23840
   Abstract »    Full Text »    PDF »
A Novel Regulatory Mechanism of the Bone Morphogenetic Protein (BMP) Signaling Pathway Involving the Carboxyl-Terminal Tail Domain of BMP Type II Receptor.
M. C. Chan, P. H. Nguyen, B. N. Davis, N. Ohoka, H. Hayashi, K. Du, G. Lagna, and A. Hata (2007)
Mol. Cell. Biol. 27, 5776-5789
   Abstract »    Full Text »    PDF »
Regulation of the Pro-apoptotic Scaffolding Protein POSH by Akt.
T. R. Lyons, J. Thorburn, P. W. Ryan, A. Thorburn, S. M. Anderson, and C. K. Kassenbrock (2007)
J. Biol. Chem. 282, 21987-21997
   Abstract »    Full Text »    PDF »
Survival Factor Withdrawal-induced Apoptosis of TF-1 Cells Involves a TRB2-Mcl-1 Axis-dependent Pathway.
K.-R. Lin, S.-F. Lee, C.-M. Hung, C.-L. Li, H.-F. Yang-Yen, and J. J. Y. Yen (2007)
J. Biol. Chem. 282, 21962-21972
   Abstract »    Full Text »    PDF »
Human Tribbles-1 Controls Proliferation and Chemotaxis of Smooth Muscle Cells via MAPK Signaling Pathways.
H. Y. Sung, H. Guan, A. Czibula, A. R. King, K. Eder, E. Heath, S. K. Suvarna, S. K. Dower, A. G. Wilson, S. E. Francis, et al. (2007)
J. Biol. Chem. 282, 18379-18387
   Abstract »    Full Text »    PDF »
TRB3 Inhibits the Transcriptional Activation of Stress-regulated Genes by a Negative Feedback on the ATF4 Pathway.
C. Jousse, C. Deval, A.-C. Maurin, L. Parry, Y. Cherasse, C. Chaveroux, R. Lefloch, P. Lenormand, A. Bruhat, and P. Fafournoux (2007)
J. Biol. Chem. 282, 15851-15861
   Abstract »    Full Text »    PDF »
Genetic Deletion of Trb3, the Mammalian Drosophila tribbles Homolog, Displays Normal Hepatic Insulin Signaling and Glucose Homeostasis.
H. Okamoto, E. Latres, R. Liu, K. Thabet, A. Murphy, D. Valenzeula, G. D. Yancopoulos, T. N. Stitt, D. J. Glass, and M. W. Sleeman (2007)
Diabetes 56, 1350-1356
   Abstract »    Full Text »    PDF »
Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure.
X.-H. Yao and B. L. Gregoire Nyomba (2007)
Am J Physiol Regulatory Integrative Comp Physiol 292, R1926-R1933
   Abstract »    Full Text »    PDF »
Large-scale phosphorylation analysis of mouse liver.
J. Villen, S. A. Beausoleil, S. A. Gerber, and S. P. Gygi (2007)
PNAS 104, 1488-1493
   Abstract »    Full Text »    PDF »
Glucose, dexamethasone, and the unfolded protein response regulate TRB3 mRNA expression in 3T3-L1 adipocytes and L6 myotubes.
S. Z. Yacoub Wasef, K. A. Robinson, M. N. Berkaw, and M. G. Buse (2006)
Am J Physiol Endocrinol Metab 291, E1274-E1280
   Abstract »    Full Text »    PDF »
Skeletal Muscle-Selective Knockout of LKB1 Increases Insulin Sensitivity, Improves Glucose Homeostasis, and Decreases TRB3.
H.-J. Koh, D. E. Arnolds, N. Fujii, T. T. Tran, M. J. Rogers, N. Jessen, Y. Li, C. W. Liew, R. C. Ho, M. F. Hirshman, et al. (2006)
Mol. Cell. Biol. 26, 8217-8227
   Abstract »    Full Text »    PDF »
Effect of TRB3 on Insulin and Nutrient-stimulated Hepatic p70 S6 Kinase Activity.
R. Matsushima, N. Harada, N. J. G. Webster, Y. M. Tsutsumi, and Y. Nakaya (2006)
J. Biol. Chem. 281, 29719-29729
   Abstract »    Full Text »    PDF »
PGC-1{alpha} and PGC-1beta have both similar and distinct effects on myofiber switching toward an oxidative phenotype.
O. H. Mortensen, L. Frandsen, P. Schjerling, E. Nishimura, and N. Grunnet (2006)
Am J Physiol Endocrinol Metab 291, E807-E816
   Abstract »    Full Text »    PDF »
Mediators of endoplasmic reticulum stress-induced apoptosis.
E. Szegezdi, S. E. Logue, A. M. Gorman, and A. Samali (2006)
EMBO Rep. 7, 880-885
   Abstract »    Full Text »    PDF »
TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism..
L. Qi, J. E. Heredia, J. Y. Altarejos, R. Screaton, N. Goebel, S. Niessen, I. X. MacLeod, C. W. Liew, R. N. Kulkarni, J. Bain, et al. (2006)
Science 312, 1763-1766
   Abstract »    Full Text »    PDF »
Peroxisome Proliferator-Activated Receptor {alpha} Activation Decreases Metastatic Potential of Melanoma Cells In vitro via Down-Regulation of Akt..
M. Grabacka, P. M. Plonka, K. Urbanska, and K. Reiss (2006)
Clin. Cancer Res. 12, 3028-3036
   Abstract »    Full Text »    PDF »
Chronic Ethanol Intake Impairs Insulin Signaling in Rats by Disrupting Akt Association with the Cell Membrane: ROLE OF TRB3 IN INHIBITION OF Akt/PROTEIN KINASE B ACTIVATION.
L. He, F. A. Simmen, H. M. Mehendale, M. J. J. Ronis, and T. M. Badger (2006)
J. Biol. Chem. 281, 11126-11134
   Abstract »    Full Text »    PDF »
Histone Acetylation-independent Effect of Histone Deacetylase Inhibitors on Akt through the Reshuffling of Protein Phosphatase 1 Complexes.
C.-S. Chen, S.-C. Weng, P.-H. Tseng, H.-P. Lin, and C.-S. Chen (2005)
J. Biol. Chem. 280, 38879-38887
   Abstract »    Full Text »    PDF »
Peroxisome proliferator-activated receptor {alpha} is required for feedback regulation of highly unsaturated fatty acid synthesis.
Y. Li, T. Y. Nara, and M. T. Nakamura (2005)
J. Lipid Res. 46, 2432-2440
   Abstract »    Full Text »    PDF »
Identification of Downregulated Messenger RNAs in Bovine Granulosa Cells of Dominant Follicles Following Stimulation with Human Chorionic Gonadotropin.
K. Ndiaye, T. Fayad, D. W. Silversides, J. Sirois, and J. G. Lussier (2005)
Biol Reprod 73, 324-333
   Abstract »    Full Text »    PDF »
A Novel Protein Kinase B (PKB)/AKT-binding Protein Enhances PKB Kinase Activity and Regulates DNA Synthesis.
M. Anai, N. Shojima, H. Katagiri, T. Ogihara, H. Sakoda, Y. Onishi, H. Ono, M. Fujishiro, Y. Fukushima, N. Horike, et al. (2005)
J. Biol. Chem. 280, 18525-18535
   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