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Gene Review

MT4  -  metallothionein 4

Homo sapiens

Synonyms: MT-4, MT-IV, MTIV, Metallothionein-4, Metallothionein-IV
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Disease relevance of MT4

  • We have analyzed the replication of Nef+ and Nef- isogenic human immunodeficiency virus in CEM, HUT78, MT4 lymphoid, and U937 monocytic cell lines [1].
  • Recombinant (E. coli ) synthesis of mammalian MT1 and MT4 domains as separate peptides in Zn(II) and Cd(II) enriched growth media has rendered metal complexes containing sulfide anions as additional ligands [2].
  • All the test compounds proved active against HIV-1 and HIV-2, their 50% inhibitory concentration (IC50) being in the range of 0.04-7.5 micrograms/mL, while they were not toxic to the host cells (CEM-4 or MT-4) at concentrations up to 100 micrograms/mL or higher [3].
  • Normal BM stromal cells were electroporated with a plasmid containing the simian virus 40 (SV40) large T antigen (SV40 T Ag) under the control of a synthetic metallothionein promoter (MT4); this construct is designated MT4 SV40 T Ag [4].
  • The 52- and 46-kDa factors are present in human T-cell lines Jurkat and MT4 (HTLV-I transformed) and in HeLa cells but are undetectable in a human placental cell line JEG-3, which gave a reduced level of trans-activation [5].

High impact information on MT4

  • Although much is known about the ontogeny of function- and specificity-associated surface molecules such as Ly2 and MT4 (the murine equivalent of human T4) during this period, the ontogeny of the T-cell antigen receptors remains obscure [6].
  • When MT-2 and MT-4 were infected with HTLV-III, the probable etiologic agent of the acquired immune deficiency syndrome (AIDS), rapid cytopathogenic effects and cytotoxicity were observed that made it possible to titrate the biologically active virus in a plaque-forming assay [7].
  • So324 has anti-HIV activity in human CEM, MT4, and monocyte/macrophage cells that is superior to that of d4T [8].
  • In the presence of 5 microM PGE2, 2.5-fold more virus were released from the infected MT-4 cells as compared to untreated control cells on day 3 after infection [9].
  • The specific expression of MT-III in the brain and of MT-IV in the squamous epithelium of skin and tongue offers a unique opportunity to identify and characterize the tissue-specific factors involved in their expression [10].

Chemical compound and disease context of MT4


Biological context of MT4

  • Further characterization of enzyme kinetics showed the binding mode of MT4 was competitive with the ATP substrate-binding site of p38alpha MAPK [16].
  • METHODS: Syncytium-inducing (SI) capacity, tropism for cell lines (MT4 and H9) and replication rate were determined in 49 HIV isolates obtained from 17 HIV seroconverters [17].
  • For example, in experiments involving proviral clones with LTRs containing one or two NF-kappa B elements (and no Sp1 binding sites), a hierarchy of cellular permissivity to virus replication (peripheral blood lymphocytes = MT4 greater than H9 greater than CEM greater than Jurkat) was observed [18].
  • PX1 and MT4 may have been selected to harbor somatic mutations that allow a bypass of the Tax-induced block in mitosis [19].
  • This contrasts with the Tax-transformed cell lines, PX1 (fibroblast) and MT4 (lymphocyte), which produce Tax at high levels, but without the accompanying late-stage cell cycle abnormalities [19].

Anatomical context of MT4

  • In the present work we used fluorescence flow cytometry to study the binding of human HRG to the human T-cell lines Jurkat and MT4, and to the murine antigen-specific T-cell clone D10, and to study the effect of divalent cations zinc and copper on this binding [20].
  • Studies using confocal fluorescence microscopy indicated that following incubation of MT4 cells with HRG in the presence of zinc at 4 degrees, the HRG was localized exclusively at the plasma membrane, but was actively internalized after incubation at 37 degrees [20].
  • MT-I and MT-II isoforms are found in the brain and in the peripheral tissues; MT-III isoform, possessing an additional seven amino acids, is expressed mostly in the brain and to a very minute extent in the intestine and pancreas; whereas MT-IV isoform is found in tissues containing stratified squamous epithelial cells [21].
  • Murine MT-IV mRNA appears to be expressed exclusively in stratified squamous epithelia associated with oral epithelia, esophagus, upper stomach, tail, footpads, and neonatal skin [22].
  • Molecular relationships of the human B cell alloantigens, MT2, MB3, MT4, and DR5 [23].

Associations of MT4 with chemical compounds

  • The Zn- and Cd-Clusters of Recombinant Mammalian MT1 and MT4 Metallothionein Domains Include Sulfide Ligands [2].
  • The MT-IV proteins are highly conserved in both species and have a glutamate insertion at position 5 relative to the classical MT-I and MT-II proteins [22].
  • The 5-halogeno-FddUrd analogues had a markedly higher affinity for MT4 thymidine kinase than FddUrd (Ki/Km, 4.0-4.7, as compared with 302 for FddUrd) [24].
  • In ATH8 cells ddCyd, ddeCyd, and ddAdo had the highest therapeutic index whereas in MT4 cells AzddThd, ddThd, ddCyd, and ddAdo were the most selective [25].
  • Variants of a lymphoblastoid cell line, LCL 526 (SB3 MB1 DR1 B44 C5 A2/SB4 MT4 DR4 B27 C2 A24), which lost various HLA specificities were selected with monoclonal antibodies and complement using a method developed by Kavathas et al [26].

Other interactions of MT4

  • Likewise, OSM did not show any anti-HIV-1 activity in the MT4 cell/MTT assay [27].
  • MT-I and MT-II are two widely expressed isoforms, while MT-III and MT-IV (isoforms recently discovered) have a more restricted expression, normally in the brain and in the keratinizing epithelia, respectively [28].
  • We demonstrate here that biologically active IL-15 is indeed detectable in a constitutively expressed, membrane-bound form on normal human monocytes, as well as on monocytic cell lines (MONO-MAC-6, THP-1, and U937), but not on human T or B cells (MT4, M9, C5966, JURKAT, DAUDI, RAJI, and Epstein-Barr virus-immortalized B-cell clones) [29].
  • The capability of a new cell line, MT4-CCR5-tat, to amplify plasma HIV-1 was also tested [30].
  • In addition, anti-beta 2m MAb were not efficient in preventing syncytium formation between HIV-infected PBMC and CD4-positive MT4 cells [31].

Analytical, diagnostic and therapeutic context of MT4

  • We have used alloantisera with carefully defined immunochemical as well as serologic specificity, and two immunochemical techniques, sequential immunoprecipitation with analysis by SDS-PAGE and two-dimensional gel electrophoresis, to explore the molecular relationships of the MT2, MB3, MT4, and HLA-DR5 antigenic determinants [23].
  • One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (9,L-696,229), which was a highly selective antagonist of the RT enzyme (IC50 = 23 nM) and which inhibited the spread of HIV-1 IIIB infection by > 95% in MT4 human T-lymphoid cell culture (CIC95 = 50-100 nM), was selected for clinical evaluation as an antiviral agent [32].
  • To more closely define the stage of SIV replication adversely affected by IFN, we used several approaches, including PCR amplification, to examine the effects of IFN on viral DNA synthesis and integration in MT4 and 174 x CEM cells synchronously infected with SIV [33].
  • After extraction and immunoblotting, the MT4 antigen was observed as three reduced species of M(r) 225, 250, and 260 [34].
  • Within the first 24 hr after amputation the MT4 antigen is localized to an acellular space beneath the wound epithelium, and first appears in the basal cells of the wound epithelium between days 5 and 7 [34].


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