Disease relevance of TXNL1

• The Escherichia coli DsbA protein, a possible PDI analogue, appears to be more structurally similar to the N-terminal thioredoxin-like domain of PDIs [1].
• A gene that may encode a novel protein disulfide oxidoreductase, designated txlA (thioredoxin-like), was isolated from the cyanobacterium Synechococcus sp. strain PCC7942 [2].
• Studies on another breast tumor cell line, ZR-57-1, also showed the schedule of EDX (0-3 h) + TXT or TXL (24-27 h) to be more synergistic than, the other two schedules examined [3].
• In vitro drug sensitivity assays have shown that the combination of TXL and CDDP is more effective in CDDP-resistant ovarian carcinoma cell lines, with different cytotoxicities depending on the sequence of drug exposure [4].
• We have established a taxol-resistant human small-cell lung cancer cell line (H69/Txl) by exposing H69 cells to stepwise increases in taxol concentration [5].

High impact information on TXNL1

• RdCVF is a truncated thioredoxin-like protein specifically expressed by photoreceptors [6].
• Eps1 has two thioredoxin-like domains containing a CPHC and a CDKC active site [7].
• PATIENTS AND METHODS: A single cycle of mobilization was used, primed with cyclophosphamide (CPA)/paclitaxel (Txl) and filgrastim (granulocyte colony-stimulating factor [G-CSF]), followed by three cycles of high-dose carboplatin (CBDCA)/Txl and one cycle of high-dose melphalan (MEL), each rescued by PBP [8].
• We propose that the PDI subunit of the complex provides electrons for reduction of the thioredoxin-like CXXC center in VKORC1 [9].
• Vit.K(1)H(2) is produced by the warfarin-sensitive enzyme vitamin K 2,3-epoxide reductase (VKOR) of the vitamin K cycle that has been shown to harbor a thioredoxin-like CXXC center involved in reduction of vitamin K(1) 2,3-epoxide (Vit.K>O) [9].

Chemical compound and disease context of TXNL1

• The dithiol/disulfide active sites of each of the two isolated thioredoxin-like domains of protein disulfide isomerase (PDI) expressed in Escherichia coli have been characterized in order to understand their catalytic mechanisms and their functions in PDI [10].
• Using two human breast cancer cell lines, MDA-MB-231 and BT-474, the antitumor effects of a combination of antisense ODN and anticancer drugs, including mitomycin C (MMC), adriamycin (ADM), paclitaxel (TXL), and docetaxel (TXT) was evaluated [11].
• Estradiol decreased sensitivity to ADM, MMC, and TXL in MCF-7 and MDA-MB-231 breast cancer cells, and this was associated in part with an increase in the amount of Bcl-2 protein, and decreases in levels of Bax and cytochrome c leading to apoptosis [12].
• We investigated the ability of different doses and durations of exposure to the chemotherapeutic drugs 1-beta-D-arabinofuranosylcytosine (Ara-C), mitoxantrone (MTN), and paclitaxel (taxol, TXL) to induce internucleosomal DNA fragmentation and apoptosis in human acute myeloid leukemia (AML) HL-60 cells in suspension culture [13].
• Oxaliplatin (OPT), a third-generation platinating agent, is currently being evaluated in a phase II clinical trial in head and neck cancer patients and in a phase I clinical trial in combination with paclitaxel (TXL) [14].

Biological context of TXNL1

• This report describes the cloning of a human cDNA that encodes a new protein (Txl, Thioredoxin-like) that belongs to the expanding family of thioredoxins based on sequence comparison of the deduced amino acid sequence [15].
• Txl is a cytosolic ubiquitously expressed protein and it has been copurified with a kinase of the STE20 family, which is proteolytically activated by caspases in apoptosis [16].
• Further, overexpression of the mutated/inactive form of the parasite enzyme in L. donovani significantly reduced their release of secretory acid phosphatases, suggesting that this single thioredoxin-like domain protein disulfide isomerase could play a critical role in the Leishmania secretory pathway [17].
• The two thioredoxin-like regions are coded by exons 1-2 and 8-9, respectively [18].
• We also observed that knockdown of the tryparedoxin TbT-PNI, a thioredoxin-like protein that facilitates electron transport to both TbCPX and TbGPXI, resulted in a reduction in growth rate [19].

Anatomical context of TXNL1

• HCF164 is a membrane-anchored thioredoxin-like protein known to be indispensable for assembly of cytochrome b(6) f in the thylakoid membranes [20].
• One hypothesis is that the disulfide bond formation is catalyzed by a thioredoxin-like protein secreted and expressed on the membrane of EBV-transformed B cells [21].
• Exposure to TXL arrested the cells in the G(2)/M phase in both cell lines [4].
• PURPOSE: Paclitaxel (Taxol, TXL) is an antimicrotubule agent that stabilizes microtubules, arrests the cell cycle at the G(2)/M phase and induces apoptosis [4].
• Human thioredoxin-like protein (hTRXL) is differentially expressed at different development stages of human fetal cerebrum and belongs to an expanding family of thioredoxins [22].

Associations of TXNL1 with chemical compounds

• Despite their complementary roles in catalysis, the thioredoxin-like centers exhibit the same dependence on the glutathione redox buffer composition as evidenced by the equivalent K(ox) values for the wild-type (47 +/- 1 microM), N-terminal mutant (43 +/- 3 microM), and C-terminal mutant (44 +/- 1 microM) [23].
• The deduced 496 amino acids contain a 17-residue NH2-terminal signal peptide, a KDEL COOH-terminal ER retention signal and two thioredoxin-like active site domains, -CGHC-, identical with those in protein disulfide isomerase (PDI) [24].
• We developed concise, accurate prediction models of the in vitro activity for 8 anticancer drugs (5-FU, CDDP, MMC, DOX, CPT-11, SN-38, TXL and TXT), along with individual clinical responses to 5-FU using expression data of 12 genes [25].
• Characterization of the active site cysteine residues of the thioredoxin-like domains of protein disulfide isomerase [10].
• A model is discussed whereby the immunoglobulin fold of DsbD(N) may provide for the discriminating interaction with thioredoxin-like factors, thereby triggering movement of the phenylalanine cap followed by disulfide rearrangement [26].

Other interactions of TXNL1

• We propose that the identification of SH3BGRL2 establishes a novel family of human genes, coding for highly conserved small proteins belonging to Thioredoxin-like protein Superfamily [27].
• SH3BGRL3 protein shows a significant similarity to Glutaredoxin 1 of Escherichia coli, and all the three proteins are predicted to belong to Thioredoxin-like protein Superfamily [27].
• The stimulatory effect of rhTNF-alpha is mediated predominantly by the 55-kDa TNF receptor because the agonistic monoclonal antibody htr-9 and the Trp32 Thr86 TNF-alpha mutant protein specific for this receptor type produced similar results to rhTNF-alpha [28].
• The structure of human thioltransferase is characterized by a thioredoxin-like fold which comprises a four-stranded central beta-sheet flanked on each side by alpha-helices [29].
• Isolation and characterization of a novel human thioredoxin-like gene hTLP19 encoding a secretory protein [30].

Analytical, diagnostic and therapeutic context of TXNL1

• Molecular cloning and expression of a cDNA encoding a human thioredoxin-like protein [15].
• Using site-directed mutagenesis, both cysteines of each of the thioredoxin-like centers, (C35S,C38S) and (C379S,C382S) were replaced by serines [23].
• Analysis of circular dichroism spectra of fragments 1-360 and 361-469 and comparison to spectra of full-length Sptrx-1 supports a two-domain organization with a largely unstructured N-terminal domain and a folded thioredoxin-like C-terminal domain [31].
• RESULTS: In both SCC VII and EL4 tumors, maximum values of mitotic index (MI) and apoptosis frequency were observed 9 and 24 h after TXL administration, respectively [32].
• METHODS: We investigated the effects and the molecular mechanisms of combination chemotherapy with TXL and CDDP in the CDDP-resistant cell line A431/CDDP2, and in its parental human epidermoid cell line A431/P [4].

References