Disease relevance of SLC7A11

• Induction of cystine-glutamate transporter xc- by human immunodeficiency virus type 1 transactivator protein tat in retinal pigment epithelium [1].
• Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpesvirus 8) binds to adherent target cell surface heparan sulfate molecules via its envelope glycoproteins gB and gpK8.1A, to integrins via gB, to the transporter CD98/xCT complex, and possibly to another molecule(s) [2].
• LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x- C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after, brain ischemia [3].
• Primary mouse ganglion cells and RGC-5 cells express xCT and 4F2hc [4].
• To examine the neuroprotective role of xCT, various non-neuronal cell types (astrocytes, meningeal cells, and peripheral fibroblasts) were cocultured with immature cortical neurons and exposed to oxidative glutamate toxicity, a model involving glutathione depletion [5].

Psychiatry related information on SLC7A11

• KSHV target cell permissiveness correlated closely with endogenous expression of xCT messenger RNA and protein in diverse human and nonhuman cell types [6].

High impact information on SLC7A11

• Baker et al. have recently studied the potential role of cocaine-induced alterations in accumbens cystine-glutamate transporter activity (which controls basal extracellular glutamate levels) during cocaine-induced relapse to drug seeking in rats [7].
• The cystine-glutamate transporter in the accumbens: a novel role in cocaine relapse [7].
• These results indicate that SLC7A11 mediates cellular uptake of L-alanosine but confers resistance to geldanamycin by supplying cystine for glutathione maintenance [8].
• Down-regulation of SLC7A11 by small interfering RNA affected drug potencies similarly to transport inhibitors [8].
• Expression of mRNA for xCT and 4F2hc subunits, which are components of the cystine/Glu antiporter, was seen in both cultured mouse metatarsals and rat costal chondrocytes [9].

Chemical compound and disease context of SLC7A11

• Kaposi's sarcoma-associated herpesvirus fusion-entry receptor: cystine transporter xCT [6].
• Functional complementary DNA selection for a receptor mediating KSHV cell fusion identified xCT, the 12-transmembrane light chain of the human cystine/glutamate exchange transporter system x-c. Expression of recombinant xCT rendered otherwise not susceptible target cells permissive for both KSHV cell fusion and virion entry [6].

Biological context of SLC7A11

• Human xCT is the seventh human member of the family of amino acid transporters that are subunits of 4F2hc or rBAT and, inview of its amino acid sequence identity (89%) with mouse xCT, is most probably the human orthologue thereof [10].
• The xCT gene consisted of twelve exons and sequence analysis identified four electrophile response element (EpRE)-like sequences between -230 and -1 in the 5'-flanking region, designated EpRE-1 to EpRE-4 [11].
• Thiol modification of cysteine 327 in the eighth transmembrane domain of the light subunit xCT of the heteromeric cystine/glutamate antiporter suggests close proximity to the substrate binding site/permeation pathway [12].
• Biotinylation of H110C was blocked by xCT substrates, by the nontransportable inhibitor (S)-4-carboxyphenylglycine, and by the impermeable reagent (2-sulfonatoethyl) methanethiosulfonate, which produced an inactivation of H110C that was protected by L-glutamate and L-cysteine with an IC(50) similar to the K(m) [13].
• The human x(c)(-) light chain (human xCT) was cloned from an ARPE-19 cell cDNA library [14].

Anatomical context of SLC7A11

• Expression of human xCT alone in oocytes did not induce amino acid transport activity and the expressed xCT protein was localised intracellularly [10].
• When human xCT was co-expressed with 4F2hc, the former localised to the oocyte plasma membrane [10].
• Depletion of GSH by the electrophile diethylmaleate (DEM) induces the activity and expression of xCT in peritoneal macrophages [15].
• We here examine the effects of vitamin C on induction of xCT by DEM in human umbilical artery smooth muscle cells [15].
• In human peripheral blood neutrophils, neither the activity of system x(c)(-) nor xCT mRNA was detected [16].

Associations of SLC7A11 with chemical compounds

• Linking expression of SLC7A11 with potency of 1,400 candidate anticancer drugs identified 39 showing positive correlations, e.g., amino acid analogue, L-alanosine, and 296 with negative correlations, e.g., geldanamycin [8].
• METHODS: The transport function of xc- was measured as glutamate uptake in the absence of Na+. mRNA levels for xCT and 4F2hc, the two subunits of system xc-, were monitored by RT-PCR and Northern blot and protein levels by Western blot [1].
• The amino acid transport activity induced by the co-expression of human 4F2hc and xCT in Xenopus oocytes was sodium independent and specific for L-cystine, L-glutamate and L-aspartate [10].
• In the present study, we have investigated the mechanism of the transcriptional regulation of xCT mRNA by diethyl maleate [11].
• We measured sensitivity to thiol modification of the heteromeric glutamate/cystine transporter 4F2hc-xCT expressed in Xenopus oocytes. p-Chloromercuribenzoate (pCMB) and p-chloromercuribenzenesulfonate (pCMBS) rapidly blocked transport activity [12].

Physical interactions of SLC7A11

• Surprisingly, xCT transport activity in HEK293 cells is not dependent on the co-expression of the exogenous 4F2hc [17].

Other interactions of SLC7A11

• Identification and characterisation of human xCT that co-expresses, with 4F2 heavy chain, the amino acid transport activity system xc- [10].

Analytical, diagnostic and therapeutic context of SLC7A11

• The expression pattern of xCT and 4F2hc in the mouse retina was analyzed by immunofluorescence [1].
• Northern blot analysis demonstrated that the expression of both xCT and 4F2hc was significantly enhanced by oxygen [18].
• Molecular cloning and expression of human xCT, the light chain of amino acid transport system xc- [18].

References