Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The GLH proteins belong to a family of four germline RNA helicases in Caenorhabditis elegans. These putative ATP-dependent enzymes localize to the P granules, which are nonmembranous complexes of protein and RNA exclusively found in the cytoplasm of all C. elegans germ cells and germ cell precursors. To determine what proteins the GLHs bind, C. elegans cDNA libraries were screened by the yeast two-hybrid method, using GLHs as bait. Three interacting proteins, CSN-5, KGB-1, and ZYX-1, were identified and further characterized. GST pull-down assays independently established that these proteins bind GLHs. CSN-5 is closely related to the subunit 5 protein of COP9 signalosomes, conserved multiprotein complexes of plants and animals. RNA interference (RNAi) with csn-5 results in sterile worms with small gonads and no oocytes, a defect essentially identical to that produced by RNAi with a combination of glh-1 and glh-4. KGB-1 is a putative JNK MAP kinase that GLHs bind. A kgb-1 deletion strain has a temperature-sensitive, sterile phenotype characterized by the absence of mature oocytes and the presence of trapped, immature oocytes that have undergone endoreplication. ZYX-1 is a LIM domain protein most like vertebrate Zyxin, a cytoskeletal adaptor protein. In C. elegans, while zyx-1 appears to be a single copy gene, neither RNAi depletion nor a zyx-1 deletion strain results in an obvious phenotype. These three conserved proteins are the first members in each of their families reported to associate with germline helicases. Similar to the loss of GLH-1 and GLH-4, loss of either CSN-5 or KGB-1 causes oogenesis to cease, but does not affect the initial assembly of P granules.
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PMID:The GLH proteins, Caenorhabditis elegans P granule components, associate with CSN-5 and KGB-1, proteins necessary for fertility, and with ZYX-1, a predicted cytoskeletal protein. 1243 62

LIM domain protein KyoT interacts with transcription factor RBP-J and modulates Notch signaling pathway. To study the function of KyoT, yeast two-hybrid was performed and proteins interacting with KyoT2 including Ring1 and hPc2 (human polycomb 2) that belong to PcG(polycomb group) were analyzed. The interactions between Ring1, hPc2, and KyoT2 were confirmed by changing vectors in two-hybrid analysis. Their interactions in vitro were confirmed by GST-pull down assay. Two-hybrid assay showed that the LIM domain of KyoT was responsible for interacting with the full-length Ring1 and hPc2. Moreover, the LIM domain also interacted with the C-terminus of hPc2. Interactions of KyoT2 with Ring1 and hPc2 suggested that PcG family might be involved in Notch signaling pathway.
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PMID:The interactions of LIM protein KyoT with polycomb proteins. 1254 15

Previously we identified TES as a candidate tumour suppressor gene that is located at human chromosome 7q31.1. More recently, we and others have shown TES to encode a novel LIM domain protein that localises to focal adhesions. Here, we present the cloning and functional analysis of the chicken orthologue of TES, cTES. The TES proteins are highly conserved between chicken and human, showing 89% identity at the amino acid level. We show that the cTES protein localised at focal adhesions, actin stress fibres, and sites of cell-cell contact, and GST-cTES can pull-down zyxin and actin. To investigate a functional role for cTES, we looked at the effect of its overexpression on cell spreading and cell motility. Cells overexpressing cTES showed increased cell spreading on fibronectin, and decreased cell motility, compared to RCAS vector transfected control cells. The data from our studies with cTES support our previous findings with human TES and further implicate TES as a member of a complex of proteins that function together to regulate cell adhesion and additionally demonstrate a role for TES in cell motility.
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PMID:Characterisation of chicken TES and its role in cell spreading and motility. 1474 47

The DNA-binding protein recombination signal-binding protein-Jk (RBP-J) plays a key role in transcriptional regulation by targeting the intracellular domain of Notch (NIC) and the Epstein-Barr virus nuclear antigen 2 (EBNA2) to specific promoters. In the absence of the Notch signaling, RBP-J acts as a transcriptional suppressor through recruiting co-suppressors such as histone deacetylase (HDAC). KyoT2 is a LIM domain protein that suppresses the RBP-J-mediated transcriptional activation. In the current study, we show that the polycomb group (PcG) protein HPC2, which functions as a transcriptional suppressor, is a candidate of KyoT2-binding proteins. To confirm the physical and functional interaction between KyoT2 and HPC2, we carried out yeast two-hybrid, GST-pull down, co-immunoprecipitation, as well as mammalian two-hybrid assays. Our results showed HPC2 and KyoT2 interacted both in vitro and in vivo, probably through the C-terminal fragment of HPC2 and LIM domains of KyoT2. In addition, we also found that overexpression of HPC2, not only inhibited transactivation of a RBP-J-dependent promoter by NIC, but also transactivation by RBP-J-VP16, a constitutively active form of RBP-J. Taken together, our results suggested that KyoT2 might inhibit the RBP-J-mediated transactivation through NIC by recruiting co-suppressors such as HPC2.
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PMID:The PcG protein HPC2 inhibits RBP-J-mediated transcription by interacting with LIM protein KyoT2. 1571 Apr 17

Extensive evidence indicates that serum response factor (SRF) regulates muscle-specific gene expression and that myocardin family SRF cofactors are critical for smooth muscle cell differentiation. In a yeast two hybrid screen for novel SRF binding partners expressed in aortic SMC, we identified four and a half LIM domain protein 2 (FHL2) and confirmed this interaction by GST pull-down and coimmunoprecipitation assays. FHL2 also interacted with all three myocardin factors and enhanced myocardin and myocardin-related transcription factor (MRTF)-A-dependent transactivation of smooth muscle alpha-actin, SM22, and cardiac atrial natriuretic factor promoters in 10T1/2 cells. The expression of FHL2 increased myocardin and MRTF-A protein levels, and, importantly, this effect was due to an increase in protein stability not due to an increase in myocardin factor mRNA expression. Treatment of cells with proteasome inhibitors MG-132 and lactacystin strongly upregulated endogenous MRTF-A protein levels and resulted in a substantial increase in ubiquitin immunoreactivity in MRTF-A immunoprecipitants. Interestingly, the expression of FHL2 attenuated the effects of RhoA and MRTF-B on promoter activity, perhaps through decreased MRTF-B nuclear localization or decreased SRF-CArG binding. Taken together, these data indicate that myocardin factors are regulated by proteasome-mediated degradation and that FHL2 regulates SRF-dependent transcription by multiple mechanisms, including stabilization of myocardin and MRTF-A.
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PMID:Regulation of myocardin factor protein stability by the LIM-only protein FHL2. 1858 95

Protein-protein interactions are critical for protein trafficking, localization and the regulation of ion channels. The human ether-a-go-go-related gene (herg) encodes the alpha-subunit of the potassium channel underlying the rapid component of the cardiac delayed rectifier current. To identify the cellular proteins involved in the regulation of the HERG channel, a human heart cDNA library was screened using a yeast two-hybrid system, with the N-terminus of HERG as bait. The four and a half LIM domain protein 2 (FHL2) was identified as a potential HERG partner. The interaction between these two proteins was confirmed by co-immunoprecipitation and glutathione transferase pull-down assays and immunocytochemical analysis. The physiological implication of HERG-FHL2 interaction, assessed by whole-cell, patch-clamp electrophysiology experiments, showed a significant increase in the HERG current amplitude and a faster deactivation of the tail current in human embryonic kidney 293 cells co-expressing HERG and FHL2. These data indicate that FHL2 interacts with and regulates the HERG channel. Our findings may aid in the further understanding of the molecular basis of HERG channel diversity and arrhythmogenesis in the long-QT syndrome.
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PMID:The four and a half LIM domain protein 2 interacts with and regulates the HERG channel. 1868 May 9

The t(10;11)(p13;q14) translocation results in the fusion of the CALM (clathrin assembly lymphoid myeloid leukemia protein) and AF10 genes. This translocation is observed in acute myeloblastic leukemia (AML M6), acute lymphoblastic leukemia (ALL) and malignant lymphoma. Using a yeast two-hybrid screen, the four and a half LIM domain protein 2 (FHL2) was identified as a CALM interacting protein. Recently, high expression of FHL2 in breast, gastric, colon, lung as well as in prostate cancer was shown to be associated with an adverse prognosis. The interaction between CALM and FHL2 was confirmed by glutathione S-transferase-pulldown assay and co-immunoprecipitation experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294-335 of CALM. The transcriptional activation capacity of FHL2 was reduced by CALM, but not by CALM/AF10, which suggests that regulation of FHL2 by CALM might be disturbed in CALM/AF10-positive leukemia. Extremely high expression of FHL2 was seen in acute erythroid leukemia (AML M6). FHL2 was also highly expressed in chronic myeloid leukemia and in AML with complex aberrant karyotype. These results suggest that FHL2 may play an important role in leukemogenesis, especially in the case of AML M6.
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PMID:FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia. 2282 78

Four and a half LIM domain protein 3 (FHL3) is a member of the FHL protein family that plays roles in the regulation of cell survival, cell adhesion and signal transduction. However, the mechanism of action for FHL3 is not yet clear. The aim of present study was to identify novel binding partner of FHL3 and to explore the underlying mechanism. With the use of yeast two-hybrid screening system, FHL3 was used as the bait to screen human fetal hepatic cDNA library for interacting proteins. Methionine-1X was identified as a novel FHL3 binding partner. The interaction between FHL3 and the full length MT-1X was further confirmed by yeast two-hybrid assay, co-immunoprecipitation and GST pull-down assays. Furthermore,the result demonstrated that MT-1X knockdown promoted the FHL3-induced inhibitory effect on HepG2 cells by regulating FHL3-mediated Smad signaling and involving in the modulation the expression of G2/M phase-related proteins through interaction with FHL3. These findings suggest that functional interactions between FHL3 and MT-1X may provide some clues to the mechanisms of FHL3-regulated cell proliferation.
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PMID:Identification and characterization of MT-1X as a novel FHL3-binding partner. 2469 Aug 79