Role of Glutaredoxin in Metabolic Oxidative Stress

Song, Jae J.; Rhee, Juong G.; Suntharalingam, Mohan; Walsh, Susan A.; Spitz, Douglas R.; Lee, Yong J.

doi:10.1074/jbc.m206826200

Cited by 235 publications

(76 citation statements)

References 48 publications

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“…This complex in turn triggers the caspase cascade, the activation of specific kinases such as the I B kinase (IKK) complex and mitogen-activated protein kinases (MAPKs), and the transcription of various genes mediated by nuclear factor-B (NF-B) and activator protein-1 (AP-1) (6 -10). Many TNF-␣ signaling pathways are activated by ROS (7,(11)(12)(13)(14)(15)(16) and attenuated by Trx overexpression (17)(18)(19)(20)(21)(22)(23)(24)(25).…”

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confidence: 99%

Roles of TRP14, a Thioredoxin-related Protein in Tumor Necrosis Factor-α Signaling Pathways

Jeong

Chang

Boja

et al. 2004

Journal of Biological Chemistry

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The possible roles of a 14-kDa human thioredoxin (Trx)-related protein (TRP14) in TNF-␣ signaling were studied in comparison with those of Trx1 by RNA interference in HeLa cells. Depletion of TRP14 augmented the TNF-␣-induced phosphorylation and degradation of I B␣ as well as the consequent activation of NF-B to a greater extent than did Trx1 depletion. Deficiency of TRP14 or Trx1 enhanced TNF-␣-induced activation of caspases and subsequent apoptosis by a similar extent. The TNF-␣-induced activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs), however, was promoted by depletion of TRP14 but not by that of Trx1. Unlike Trx1, TRP14 neither associated with nor inhibited the kinase activity of apoptosis signal-regulating kinase-1 (ASK1), an upstream activator of JNK and p38. In combination with the results in the accompanying paper that TRP14 did not reduce the known substrates of Trx1, these results suggest that TRP14 modulates TNF-␣ signaling pathways, provably by interacting with proteins distinct from the targets of Trx1. In an effort to identify target proteins of TRP14, a mutant of TRP14, in which the active site cysteine (Cys 46 ) was substituted with serine, was shown to form a disulfide-linked complex with LC8 cytoplasmic dynein light chain. The complex was detected in HeLa cells treated with H 2 O 2 or TNF-␣ but not in untreated cells, suggesting that LC8 cytoplasmic dynein light chain is a possible substrate of TRP14.The cellular redox state is affected not only by normal respiration and metabolism but also by the transient production of reactive oxygen species (ROS) 1 that results from the ligation of various cell surface receptors (1-3). Tumor necrosis factor-␣ (TNF-␣) was one of the first receptor ligands shown to generate ROS in nonphagocytic cells and is among the ligands whose signaling pathways have been studied most in relation to ROS production (4, 5). The binding of TNF-␣ to TNF receptor 1 (TNFR1) generates both proapoptotic and prosurvival signals by inducing the formation of a multiprotein signaling complex at the cell membrane. This complex in turn triggers the caspase cascade, the activation of specific kinases such as the I B kinase (IKK) complex and mitogen-activated protein kinases (MAPKs), and the transcription of various genes mediated by nuclear factor-B (NF-B) and activator protein-1 (AP-1) (6 -10). Many TNF-␣ signaling pathways are activated by ROS (7, 11-16) and attenuated by Trx overexpression (17-25).In the accompanying study (26), we identified and characterized a 14-kDa cytosolic protein, designated Trx-related protein 14 (TRP14). Here we studied the possible roles of TRP14 in TNF-␣ signaling in comparison with those of Trx1 by RNA interference (RNAi) in HeLa cells. Partial depletion of TRP14 or Trx1 by RNAi resulted in enhancement of TNF-␣-induced activation of caspases and NF-B. The TNF-␣-induced activation of c-Jun-N-terminal kinase (JNK) and p38 MAPK, however, was augmented by depletion of TRP14 but not by that of Trx1. Furthermore, unl...

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confidence: 99%

Roles of TRP14, a Thioredoxin-related Protein in Tumor Necrosis Factor-α Signaling Pathways

Jeong

Chang

Boja

et al. 2004

Journal of Biological Chemistry

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“…ASK1 activity appears to be enhanced by its binding to a number of important regulatory proteins, such as TRAFs Liu et al, 2000), Daxx (Chang et al, 1998), and JSAP1/JIP3 (Matsuura et al, 2002). On the other hand, ASK1 activity is suppressed in cells via its interaction with several prosurvival regulatory proteins, including thioredoxin (Gotoh and Cooper, 1998;Saitoh et al, 1998), glutaradoxin (Song et al, 2002), HSP72 (Park et al, 2002), Raf-1 (Chen et al, 2001), and 14-3-3 (Zhang et al, 1999). Interestingly, the binding of 14-3-3 proteins to ASK1 is phosphorylation-dependent.…”

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confidence: 99%

Negative control of apoptosis signal-regulating kinase 1 through phosphorylation of Ser-1034

et al. 2004

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“…It is possible that hD53L1 may act as a competitive inhibitor of 14-3-3 or Grx proteins that bind to the C-terminal portion of ASK1 and suppress its activation (16,17,44), resulting in prevention of 14-3-3 proteins or Grx from binding to ASK1 in a concentrationdependent manner. This possible role of hD53L1 as an inhibitor of ASK1-inhibiting proteins may explain why the kinase activity of ASK1 is not induced significantly.…”

Section: Discussionmentioning

confidence: 99%

“…This stronger effect by H 2 O 2 may be mainly due to multiple roles of H 2 O 2 for regulation of ASK1. There are two identified pathways for activation of ASK1 by H 2 O 2 : glutathione-dependent Grx-ASK1 and glutathione-independent Trx-ASK1 pathways (14,16,44). Those two H 2 O 2 -sensing proteins, Trx and Grx, bind and inhibit ASK1 under reduced conditions.…”

Section: Discussionmentioning

confidence: 99%

“…In resting cells, ASK1 constantly forms an inactive complex with Trx, but upon treatment of cells with TNF-␣ or reactive oxygen species such as H 2 O 2 , ASK1 is dissociated from Trx and activated by subsequent modifications, including oligomerization and auto-and/or cross-phosphorylation (10,14,15). It was recently reported that 14-3-3 proteins and Grx directly bind to ASK1, and that overexpression of 14-3-3 and Grx proteins blocked ASK1-induced apoptosis and JNK1 activity, respectively (16,17). In addition, protein serine/ threonine phosphatase 5 was identified as a negative regulator of the activated ASK1.…”

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confidence: 99%

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Positive Regulation of Apoptosis Signal-regulating Kinase 1 by hD53L1

Cho

Kim

et al. 2004

Journal of Biological Chemistry

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Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase family member that plays a central role in cytokine-and stressinduced apoptosis by activating c-Jun N-terminal kinase and p38 signaling cascades. ASK1-induced apoptotic activity is up-regulated by two cellular factors, Daxx and TRAF2, through direct protein-protein interactions. Daxx and TRAF2 are death receptor-associated proteins in Fas and tumor necrosis factor-␣ pathways, respectively. Recent studies suggest that calcium signaling may regulate ASK1 pathway. Here we report that human D53L1, a member of the tumor protein D52 family involved in cell proliferation and calcium signaling, up-regulates the ASK1-induced apoptosis. The human D53L1 physically interacts with the C-terminal regulatory domain of ASK1 and promotes ASK1-induced apoptotic activity by activating caspase signaling in mammalian cells. In luciferase reporter assays, hD53L1 activates c-Jun N-terminal kinase-mediated transactivation in the presence of ASK1. Expression of hD53L1 enhances autophosphorylation and kinase activity of ASK1 but has no effect on ASK1 oligomerization that is necessary for kinase activity and on binding of ASK1 to MKK6, a downstream factor of ASK1. Taken together, these results suggest that activation of ASK1 by hD53L1 may provide a novel mechanism for ASK1 regulation.

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Role of Glutaredoxin in Metabolic Oxidative Stress

Cited by 235 publications

References 48 publications

Roles of TRP14, a Thioredoxin-related Protein in Tumor Necrosis Factor-α Signaling Pathways

Roles of TRP14, a Thioredoxin-related Protein in Tumor Necrosis Factor-α Signaling Pathways

Negative control of apoptosis signal-regulating kinase 1 through phosphorylation of Ser-1034

Positive Regulation of Apoptosis Signal-regulating Kinase 1 by hD53L1

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