Circulation Research. 2002;90:1259-1266
Published online before print May 16, 2002, doi: 10.1161/01.RES.0000022160.64355.62
Published online before print May 16, 2002, doi: 10.1161/01.RES.0000022160.64355.62
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2002 American Heart Association, Inc.
Molecular Medicine |
Thioredoxin Promotes ASK1 Ubiquitination and Degradation to Inhibit ASK1-Mediated Apoptosis in a Redox Activity-Independent Manner
From the Center for Cardiovascular Research, University of Rochester Medical Center, Rochester, NY.
Correspondence to Dr Wang Min, Center for Cardiovascular Research, University of Rochester Medical Center, 601 Elmwood Ave, Box 679, Rochester, NY 14642. E-mail wang.min{at}rochester.edu
It has been shown that thioredoxin (Trx) in a reduced form binds to and inhibits apoptosis signal-regulating kinase 1 (ASK1). Apoptotic stimuli such as tumor necrosis factor (TNF) and reactive oxygen species (ROS) activate ASK1 in part by oxidizing Trx (forming intramolecular disulfide between C32 and C35) to release Trx from ASK1. In the present study, we examined if Trx affects ASK1 protein stability and whether the redox activity of Trx is critical in regulating ASK1 activity. First, we showed that overexpression of the wild-type Trx (Trx-WT) in endothelial cells induced ASK1 ubiquitination and degradation. Trx-induced ASK1 ubiquitination/degradation could be blocked by ASK1 activators TNF and TRAF2. We then tested the single-mutation of Trx at the catalytic site C32 or C35 (Trx-C32S or Trx-C35S) and the double-mutation (Trx-CS). The results showed that the single mutants (but not Trx-CS) retained the binding activity for ASK1 and the ability to induce ASK1 ubiquitination/degradation. Unlike Trx-WT, Trx-C32S and Trx-C35S mutants constitutively bind to ASK1 even in the presence of hydrogen peroxide in vitro and TNF in vivo. Finally, we showed that the single mutants (not Trx-WT) significantly (n=4 and P<0.05) inhibited ASK1-induced JNK activation, caspase 3 activity, and apoptosis in TNF/ROS-resistant manner. Our data suggest that association of Trx with ASK1 through a single Cysteine (C32 or C35) is necessary and sufficient for Trx activity in inducing ASK1 ubiquitination/degradation leading to inhibition of ASK1-induced apoptosis.
Key Words: apoptosis signal-regulating kinase 1 • thioredoxin • apoptosis • ubiquitination • tumor necrosis factor-&agr
This article has been cited by other articles:
 |
|
 |
|
  S. Piccirillo, G. Filomeni, B. Brune, G. Rotilio, and M. R. Ciriolo Redox Mechanisms Involved in the Selective Activation of Nrf2-mediated Resistance Versus p53-dependent Apoptosis in Adenocarcinoma Cells J. Biol. Chem., October 2, 2009; 284(40): 27721 - 27733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Nadeau, S. J. Charette, and J. Landry REDOX Reaction at ASK1-Cys250 Is Essential for Activation of JNK and Induction of Apoptosis Mol. Biol. Cell, August 15, 2009; 20(16): 3628 - 3637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yu, W. Min, Y. He, L. Qin, H. Zhang, A. M. Bennett, and H. Chen JAK2 and SHP2 Reciprocally Regulate Tyrosine Phosphorylation and Stability of Proapoptotic Protein ASK1 J. Biol. Chem., May 15, 2009; 284(20): 13481 - 13488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dai, Y. He, H. Zhang, L. Yu, T. Wan, Z. Xu, D. Jones, H. Chen, and W. Min Endothelial-Specific Expression of Mitochondrial Thioredoxin Promotes Ischemia-Mediated Arteriogenesis and Angiogenesis Arterioscler Thromb Vasc Biol, April 1, 2009; 29(4): 495 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kolliputi and A. B. Waxman IL-6 Cytoprotection in Hyperoxic Acute Lung Injury Occurs via Suppressor of Cytokine Signaling-1-Induced Apoptosis Signal-Regulating Kinase-1 Degradation Am. J. Respir. Cell Mol. Biol., March 1, 2009; 40(3): 314 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ebrahimian, M. R. Sairam, E. L. Schiffrin, and R. M. Touyz Cardiac hypertrophy is associated with altered thioredoxin and ASK-1 signaling in a mouse model of menopause Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1481 - H1488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sato, Y. Hoshino, T. Hara, S. Muro, H. Nakamura, M. Mishima, and J. Yodoi Thioredoxin-1 Ameliorates Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 380 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. Chen, C.-F. Lin, W.-T. Chang, W.-C. Huang, C.-F. Teng, and Y.-S. Lin Ceramide induces p38 MAPK and JNK activation through a mechanism involving a thioredoxin-interacting protein-mediated pathway Blood, April 15, 2008; 111(8): 4365 - 4374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Min, Y. Lin, S. Tang, L. Yu, H. Zhang, T. Wan, T. Luhn, H. Fu, and H. Chen AIP1 Recruits Phosphatase PP2A to ASK1 in Tumor Necrosis Factor-Induced ASK1-JNK Activation Circ. Res., April 11, 2008; 102(7): 840 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hou, S. Torii, N. Saito, M. Hosaka, and T. Takeuchi Reactive Oxygen Species-Mediated Pancreatic {beta}-Cell Death Is Regulated by Interactions between Stress-Activated Protein Kinases, p38 and c-Jun N-Terminal Kinase, and Mitogen-Activated Protein Kinase Phosphatases Endocrinology, April 1, 2008; 149(4): 1654 - 1665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Berk Atheroprotective Signaling Mechanisms Activated by Steady Laminar Flow in Endothelial Cells Circulation, February 26, 2008; 117(8): 1082 - 1089. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fujino, T. Noguchi, A. Matsuzawa, S. Yamauchi, M. Saitoh, K. Takeda, and H. Ichijo Thioredoxin and TRAF Family Proteins Regulate Reactive Oxygen Species-Dependent Activation of ASK1 through Reciprocal Modulation of the N-Terminal Homophilic Interaction of ASK1 Mol. Cell. Biol., December 1, 2007; 27(23): 8152 - 8163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Malagnac, B. Klapholz, and P. Silar PaTrx1 and PaTrx3, Two Cytosolic Thioredoxins of the Filamentous Ascomycete Podospora anserina Involved in Sexual Development and Cell Degeneration Eukaryot. Cell, December 1, 2007; 6(12): 2323 - 2331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Kutuzov, A. V. Andreeva, and T. A. Voyno-Yasenetskaya Regulation of apoptosis signal-regulating kinase 1 degradation by G{alpha}13 FASEB J, November 1, 2007; 21(13): 3727 - 3736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Nadeau, S. J. Charette, M. B. Toledano, and J. Landry Disulfide Bond-mediated Multimerization of Ask1 and Its Reduction by Thioredoxin-1 Regulate H2O2-induced c-Jun NH2-terminal Kinase Activation and Apoptosis Mol. Biol. Cell, October 1, 2007; 18(10): 3903 - 3913. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Karunakaran, L. Diwakar, U. Saeed, V. Agarwal, S. Ramakrishnan, S. Iyengar, and V. Ravindranath Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson's disease: protection by {alpha}-lipoic acid FASEB J, July 1, 2007; 21(9): 2226 - 2236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Satoh, C. M. Matter, H. Ogita, K. Takeshita, C.-Y. Wang, G. W. Dorn II, and J. K. Liao Inhibition of Apoptosis-Regulated Signaling Kinase-1 and Prevention of Congestive Heart Failure by Estrogen Circulation, June 26, 2007; 115(25): 3197 - 3204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. E. Tissing, M. L. den Boer, J. P. P. Meijerink, R. X. Menezes, S. Swagemakers, P. J. van der Spek, S. E. Sallan, S. A. Armstrong, and R. Pieters Genomewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells Blood, May 1, 2007; 109(9): 3929 - 3935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. Mehta and K. K. Griendling Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system Am J Physiol Cell Physiol, January 1, 2007; 292(1): C82 - C97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Schulze, H. Liu, E. Choe, J. Yoshioka, A. Shalev, K. D. Bloch, and R. T. Lee Nitric Oxide-Dependent Suppression of Thioredoxin-Interacting Protein Expression Enhances Thioredoxin Activity Arterioscler Thromb Vasc Biol, December 1, 2006; 26(12): 2666 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tao, X. Jiao, E. Gao, W. B. Lau, Y. Yuan, B. Lopez, T. Christopher, S. P. RamachandraRao, W. Williams, G. Southan, et al. Nitrative Inactivation of Thioredoxin-1 and Its Role in Postischemic Myocardial Apoptosis Circulation, September 26, 2006; 114(13): 1395 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Patwari, L. J. Higgins, W. A. Chutkow, J. Yoshioka, and R. T. Lee The Interaction of Thioredoxin with Txnip: EVIDENCE FOR FORMATION OF A MIXED DISULFIDE BY DISULFIDE EXCHANGE J. Biol. Chem., August 4, 2006; 281(31): 21884 - 21891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-M. Shen and S. Pervaiz TNF receptor superfamily-induced cell death: redox-dependent execution FASEB J, August 1, 2006; 20(10): 1589 - 1598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. He, W. Zhang, R. Zhang, H. Zhang, and W. Min SOCS1 Inhibits Tumor Necrosis Factor-induced Activation of ASK1-JNK Inflammatory Signaling by Mediating ASK1 Degradation J. Biol. Chem., March 3, 2006; 281(9): 5559 - 5566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Xiang, T. Seki, M. D. Schuster, P. Witkowski, A. J. Boyle, F. See, T. P. Martens, A. Kocher, H. Sondermeijer, H. Krum, et al. Catalytic Degradation of Vitamin D Up-regulated Protein 1 mRNA Enhances Cardiomyocyte Survival and Prevents Left Ventricular Remodeling after Myocardial Ischemia J. Biol. Chem., November 25, 2005; 280(47): 39394 - 39402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Noguchi, K. Takeda, A. Matsuzawa, K. Saegusa, H. Nakano, J. Gohda, J.-i. Inoue, and H. Ichijo Recruitment of Tumor Necrosis Factor Receptor-associated Factor Family Proteins to Apoptosis Signal-regulating Kinase 1 Signalosome Is Essential for Oxidative Stress-induced Cell Death J. Biol. Chem., November 4, 2005; 280(44): 37033 - 37040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Al-Lamki, J. Wang, P. Vandenabeele, J. A. Bradley, S. Thiru, D. Luo, W. Min, J. S. Pober, and J. R. Bradley TNFR1- and TNFR2-mediated signaling pathways in human kidney are cell type-specific and differentially contribute to renal injury FASEB J, October 1, 2005; 19(12): 1637 - 1645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-H. Cha, S. Kim, J. Park, E. Lee, M. Kim, S. B. Lee, J. M. Kim, J. Chung, and K. S. Cho Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila PNAS, July 19, 2005; 102(29): 10345 - 10350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhang, S. Zheng, P. Storz, and W. Min Protein Kinase D Specifically Mediates Apoptosis Signal-regulating Kinase 1-JNK Signaling Induced by H2O2 but Not Tumor Necrosis Factor J. Biol. Chem., May 13, 2005; 280(19): 19036 - 19044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, R. Zhang, D. Luo, S.-J. Park, Q. Wang, Y. Kim, and W. Min Tumor Necrosis Factor {alpha}-induced Desumoylation and Cytoplasmic Translocation of Homeodomain-interacting Protein Kinase 1 Are Critical for Apoptosis Signal-regulating Kinase 1-JNK/p38 Activation J. Biol. Chem., April 15, 2005; 280(15): 15061 - 15070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jekell, A. Hossain, U. Alehagen, U. Dahlstrom, and A. Rosen Elevated circulating levels of thioredoxin and stress in chronic heart failure Eur J Heart Fail, December 1, 2004; 6(7): 883 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhou, J. S. Boomer, and T.-H. Tan Protein Phosphatase 4 Is a Positive Regulator of Hematopoietic Progenitor Kinase 1 J. Biol. Chem., November 19, 2004; 279(47): 49551 - 49561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sugita, H. Sugita, and M. Kaneki Increased Insulin Receptor Substrate 1 Serine Phosphorylation and Stress-Activated Protein Kinase/c-Jun N-Terminal Kinase Activation Associated With Vascular Insulin Resistance in Spontaneously Hypertensive Rats Hypertension, October 1, 2004; 44(4): 484 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Lowenstein Exogenous Thioredoxin Reduces Inflammation in Autoimmune Myocarditis Circulation, September 7, 2004; 110(10): 1178 - 1179. [Full Text] [PDF]
|
|
|
|
|
|
J. Haendeler, J. Hoffmann, A. M. Zeiher, and S. Dimmeler Antioxidant Effects of Statins via S-Nitrosylation and Activation of Thioredoxin in Endothelial Cells: A Novel Vasculoprotective Function of Statins Circulation, August 17, 2004; 110(7): 856 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tao, E. Gao, N. S. Bryan, Y. Qu, H.-R. Liu, A. Hu, T. A. Christopher, B. L. Lopez, J. Yodoi, W. J. Koch, et al. Cardioprotective effects of thioredoxin in myocardial ischemia and reperfusion: Role of S-nitrosation PNAS, August 3, 2004; 101(31): 11471 - 11476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Schulze, J. Yoshioka, T. Takahashi, Z. He, G. L. King, and R. T. Lee Hyperglycemia Promotes Oxidative Stress through Inhibition of Thioredoxin Function by Thioredoxin-interacting Protein J. Biol. Chem., July 16, 2004; 279(29): 30369 - 30374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zhang, R. Al-Lamki, L. Bai, J. W. Streb, J. M. Miano, J. Bradley, and W. Min Thioredoxin-2 Inhibits Mitochondria-Located ASK1-Mediated Apoptosis in a JNK-Independent Manner Circ. Res., June 11, 2004; 94(11): 1483 - 1491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. B. Arnold, K. Ketterer, J. Kleeff, H. Friess, M. W. Buchler, and M. Korc Thioredoxin Is Downstream of Smad7 in a Pathway That Promotes Growth and Suppresses Cisplatin-Induced Apoptosis in Pancreatic Cancer Cancer Res., May 15, 2004; 64(10): 3599 - 3606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. Goldman, L. Chen, and H. Fu Activation of Apoptosis Signal-regulating Kinase 1 by Reactive Oxygen Species through Dephosphorylation at Serine 967 and 14-3-3 Dissociation J. Biol. Chem., March 12, 2004; 279(11): 10442 - 10449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. H. Watson, X. Yang, Y. E. Choi, D. P. Jones, and J. P. Kehrer Thioredoxin and Its Role in Toxicology Toxicol. Sci., March 1, 2004; 78(1): 3 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Karimi, L. X. Wang, J. M. Hammel, C. E. Mascio, M. Abdulhamid, E. W. Barner, T. D. Scholz, J. L. Segar, W. G. Li, S. D. Niles, et al. Neonatal vulnerability to ischemia and reperfusion: Cardioplegic arrest causes greater myocardial apoptosis in neonatal lambs than in mature lambs J. Thorac. Cardiovasc. Surg., February 1, 2004; 127(2): 490 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Jeong, T.-S. Chang, E. S. Boja, H. M. Fales, and S. G. Rhee Roles of TRP14, a Thioredoxin-related Protein in Tumor Necrosis Factor-{alpha} Signaling Pathways J. Biol. Chem., January 30, 2004; 279(5): 3151 - 3159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Izumi, S. Kim, M. Yoshiyama, Y. Izumiya, K. Yoshida, A. Matsuzawa, H. Koyama, Y. Nishizawa, H. Ichijo, J. Yoshikawa, et al. Activation of Apoptosis Signal-Regulating Kinase 1 in Injured Artery and Its Critical Role in Neointimal Hyperplasia Circulation, December 2, 2003; 108(22): 2812 - 2818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamawaki, J. Haendeler, and B. C. Berk Thioredoxin: A Key Regulator of Cardiovascular Homeostasis Circ. Res., November 28, 2003; 93(11): 1029 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. He, Y. Liu, V. Sharma, R. T. Dirksen, R. Waugh, S.-S. Sheu, and W. Min ASK1 Associates with Troponin T and Induces Troponin T Phosphorylation and Contractile Dysfunction in Cardiomyocytes Am. J. Pathol., July 1, 2003; 163(1): 243 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Pan, P. An, R. Zhang, X. He, G. Yin, and W. Min Etk/Bmx as a Tumor Necrosis Factor Receptor Type 2-Specific Kinase: Role in Endothelial Cell Migration and Angiogenesis Mol. Cell. Biol., November 1, 2002; 22(21): 7512 - 7523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H. Bishopric and K. A. Webster Preventing Apoptosis With Thioredoxin: ASK Me How Circ. Res., June 28, 2002; 90(12): 1237 - 1239. [Full Text] [PDF]
|
|