Thioredoxin-related Protein 32 (TRP32) Specifically Reduces Oxidized Phosphatase of Regenerating Liver (PRL)

Ishii, Tasuku; Funato, Yosuke; Miki, Hiroaki

doi:10.1074/jbc.m112.418004

Cited by 30 publications

(25 citation statements)

References 26 publications

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“…In case of both helminths the protein was present in the E/S products of the parasites [13, Brattig et al, unpublished]. The molecular mass (30–33 kDa) as well as the proteins structure suggested similar functions to those of the human Trx-related protein (TRP32), also known as TXNL-1, which protects the cell against glucose deprivation-induced cytotoxicity and is involved in antiapoptotic signaling [47, 48, 71]. Like SrTrx- and TsTrx-lp, TRP32 consists of an N-terminal Trx and a C-terminal PITH domain as well [44].…”

Section: Discussionmentioning

confidence: 99%

“…Besides thiol-based redox control, eukaryotic Trx-lps are also involved in signaling processes as cofactors of certain enzymes, regulating specific signal proteins [45, 46]. For example, the human Trx-related protein (TRP32), known as TXNL-1, protects the cell against glucose deprivation-induced cytotoxicity and is involved in activation of antiapoptotic Akt/PI3K signaling as well as PTEN (phosphatase and tensin homologue deleted on chromosome ten) inhibition [47, 48]. Another example is the thioredoxin domain containing 17 (TXNDC17), also known as Trx-related protein of 14 kDa (TRP14), which is STAT-3-dependent and responsible for the drug resistance in human colorectal cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Multifunctional Thioredoxin-Like Protein from the Gastrointestinal Parasitic NematodesStrongyloides rattiandTrichuris suisAffects Mucosal Homeostasis

Ditgen

Anandarajah

Hansmann

et al. 2016

Journal of Parasitology Research

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The cellular redox state is important for the regulation of multiple functions and is essential for the maintenance of cellular homeostasis and antioxidant defense. In the excretory/secretory (E/S) products of Strongyloides ratti and Trichuris suis sequences for thioredoxin (Trx) and Trx-like protein (Trx-lp) were identified. To characterize the antioxidant Trx-lp and its interaction with the parasite's mucosal habitat, S. ratti and T. suis Trx-lps were cloned and recombinantly expressed. The primary antioxidative activity was assured by reduction of insulin and IgM. Further analysis applying an in vitro mucosal 3D-cell culture model revealed that the secreted Trx-lps were able to bind to monocytic and intestinal epithelial cells and induce the time-dependent release of cytokines such as TNF-α, IL-22, and TSLP. In addition, the redox proteins also possessed chemotactic activity for monocytic THP-1 cells and fostered epithelial wound healing activity. These results confirm that the parasite-secreted Trx-lps are multifunctional proteins that can affect the host intestinal mucosa.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multifunctional Thioredoxin-Like Protein from the Gastrointestinal Parasitic NematodesStrongyloides rattiandTrichuris suisAffects Mucosal Homeostasis

Ditgen

Anandarajah

Hansmann

et al. 2016

Journal of Parasitology Research

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“…Within cells, oxidized proteins are reduced by thioredoxin (TRX) or TRX-related proteins using electrons donated by the glutathione and TRX reductases (TrxR), which use the electrons supplied by the NADH. In this context, TRP32 (a TRX-related protein) reduces the PRLs protecting them from oxidation and, in consequence, maintaining their activity and thus contributing to cancer progression and metastasis [34]. …”

Section: Prl-3 Posttranslational Modifications and Regulatorsmentioning

confidence: 99%

Regulatory mechanisms of phosphatase of regenerating liver (PRL)-3

Rubio

Köhn

2016

Biochemical Society Transactions

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The phosphatase of regenerating liver (PRL)-3 is overexpressed in many human cancer types and tumor metastases when compared with healthy tissues. Different pathways and mechanisms have been suggested to modulate PRL-3 expression levels and activity, giving some valuable insights but still leaving an incomplete picture. Investigating these mechanisms could provide new targets for therapeutic drug development. Here, we present an updated overview and summarize recent findings concerning the different PRL-3 expression regulatory mechanisms and posttranslational modifications suggested to modulate the activity, localization, or stability of this phosphatase.

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“…Indeed, both PRL-1and 3 have been found to associate with the plasma membrane and early endosome in mammalian cell lines (9,10,11,12,13). PRL has also been shown to be regulated by the redox status of its active site and the formation of a disulfide bond when fully oxidized (14,15,16). Since its discovery, the PRL family has been studied extensively in cell culture and in several model animal systems.…”

Section: Prl Structural Featuresmentioning

confidence: 99%

Phosphatase of regenerating liver: a novel target for cancer therapy

Campbell

Zhang

2014

Expert Opinion on Therapeutic Targets

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Importance in the Field Phosphatases of Regenerating Liver (PRLs) are novel oncogenes that interact with many, well-established cell signaling pathways that are misregulated in cancer and is known to drive cancer metastasis when overexpressed. Areas Covered in this Review This review will cover basic information of the discovery and characteristics of the PRL family. We will also report findings on the role of PRL in cancer, cell functions, and cell signaling. Furthermore, PRL’s suitability as a novel drug target will be discussed along with current methods being developed to facilitate PRL inhibition. Expert Opinion PRLs show great potential as novel drug targets for anti-cancer therapeutics. Studies indicate that PRL can perturb major cancer pathways such as Src/ERK1/2 and PTEN/PI3K/Akt. Upregulation of PRLs has also been shown to drive cancer metastasis. However, in order to fully realize its therapeutic potential, a deeper understanding of the function of PRL in normal tissue and in cancer must be obtained. Novel and integrated biochemical, chemical biological and genetic approaches will be needed to identify PRL substrate(s) and to provide proof-of-concept data on the druggability of the PRL phosphatases.

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Thioredoxin-related Protein 32 (TRP32) Specifically Reduces Oxidized Phosphatase of Regenerating Liver (PRL)

Cited by 30 publications

References 26 publications

Multifunctional Thioredoxin-Like Protein from the Gastrointestinal Parasitic NematodesStrongyloides rattiandTrichuris suisAffects Mucosal Homeostasis

Multifunctional Thioredoxin-Like Protein from the Gastrointestinal Parasitic NematodesStrongyloides rattiandTrichuris suisAffects Mucosal Homeostasis

Regulatory mechanisms of phosphatase of regenerating liver (PRL)-3

Phosphatase of regenerating liver: a novel target for cancer therapy

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