Disease relevance of ELK3

• The secreted aspartyl proteinases Sap1 and Sap2 cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium [1].
• Several complementary DNAs (cDNAs) coding for sphingolipid activator protein-2 (SAP-2) were isolated from a lambda gt-11 human hepatoma library by means of polyclonal antibodies [2].
• SAP2 and the SAP4 to SAP6 subfamily were the predominant proteinase genes expressed in the oral cavities of both Candida carriers and patients with oral candidiasis; SAP4, SAP5, or SAP6 mRNA was detected in all subjects [3].
• In this study a progressive SAP expression in the order SAP1 and SAP2 > SAP8 > SAP6 > SAP3 was observed in an in vitro model of cutaneous candidiasis based on reconstituted human epidermis [4].
• Studies on a sphingolipid activator protein (SAP-2) in fibroblasts from patients with lysosomal storage diseases, including Niemann-Pick disease Type C [5].

Psychiatry related information on ELK3

• Neural correlates of impulsive responding in borderline personality disorder: ERP evidence for reduced action monitoring [6].
• The development of visual- and auditory processing in Rett syndrome: an ERP study [7].

High impact information on ELK3

• The nucleotide sequence of the largest cDNA was colinear with the derived amino acid sequence of SAP-2 and with the nucleotide sequence of the cDNA coding for the 70-kilodalton precursor of SAP-1 (SAP precursor cDNA) [2].
• Both SAP-1 and SAP-2 appeared to be derived by proteolytic processing from a common precursor that is coded by a genetic locus on human chromosome 10 [2].
• Net (ERP/SAP2) one of the Ras-inducible TCFs, has a novel inhibitory domain with resemblance to the helix-loop-helix motif [8].
• However, within the B-cell lineage, ERP is highly expressed primarily at early stages of B-lymphocyte development, and expression declines drastically upon B-cell maturation, correlating with the enhancer activity of the IgH pi site [9].
• We have cloned the gene for a new ets-related transcription factor, ERP (ets-related protein), from the murine pre-B cell line BASC 6C2 and from mouse lung tissue [9].

Chemical compound and disease context of ELK3

• Overall the participants with Rett syndrome had longer ERP latencies and smaller ERP amplitudes than the Control group suggesting slowed information processing and reduced brain activation [7].

Biological context of ELK3

• These data suggest that SAP1, SAP2, and SAP3 all contribute to the overall virulence of C. albicans and presumably all play important roles during disseminated infections [10].
• Removal of the carboxy terminus enables ERP to interact with a variety of ets-binding sites including the E74 site, the IgH enhancer pi site, and the lck promoter ets site, suggesting a carboxy-terminal negative regulatory domain [9].
• The complete amino acid sequence of the 81 residues in SAP-2 has been determined [11].
• beta-Glucosidase activator (SAP-2) is a family of heat-stable, acidic glycoproteins which stimulate enzymatic hydrolysis of glucosylceramide [11].
• The cDNA, designed SAP-1/SAP-2 cDNA, hybridizes with two human mRNA species of approximately 3 kb in length, which most probably arise from polyadenylation at different sites [12].

Anatomical context of ELK3

• ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development [9].
• In pulse-chase experiments using antisera raised against SAP-1 or SAP-2, no cross-reacting material could be detected in the patients' fibroblasts [13].
• Only Sap2 was found to contribute to the ability of C. albicans to damage endothelial cells and stimulate them to express E-selectin [14].
• Polyclonal anti-SAP-1 and SAP-2 antisera confirmed the tissue-specificity and revealed the subcellular localization of SAPs in large granules concentrated in the apical part of the gut epithelial cells of the parasite [15].
• Recombinant SAP-2 of F. hepatica has been shown to induce lysis of human erythrocytes and peripheral blood mononuclear cells [15].

Associations of ELK3 with chemical compounds

• When expressed separately, full length SAP1, SAP2, or the NH2-terminal domain alone, are able to assemble into filaments [16].
• Secretion of SAP2 was significantly enhanced by addition of AlCl3 but not of KCl, LiCl, CaCl2, MgCl2, mannitol or sucrose to suspension cultures [17].
• In the absence of T258A and S259A mutations, alanine substitution of all other potential phosphosites within the hNET did not block PKC-induced phosphorylation and down-regulation [18].
• Saturable concentration- and time-dependent binding of mucin to C. albicans was abrogated by pronase or Sap2p treatment of mucin but was unaffected by beta-mercaptoethanol, sodium periodate, neuraminidase, lectins, or potentially inhibitory sugars [19].
• Only ritonavir and saquinavir inhibited Sap2p, Sapt1p, Sapp1p, and Saplp in micromolar concentrations [20].

Other interactions of ELK3

• These data provide further evidence for a crucial role of Sap1 and Sap2 in C. albicans vaginal infections [1].
• Sap1, Sap2 and Sap3 isoenzymes were found to be related to the vaginopathic potential of C. albicans; Sap4, Sap5 and Sap6 isoenzymes were found to be correlated with systemic infections [21].
• The amino-terminal amino acid sequences of SAP2 (57 kDa), SAP4 (21 kDa), SAP5 (19 kDa) and SAP6 (17 kDa) were homologous to the sequences of proline-rich proteins, indicating that proline-rich proteins are secreted specifically by these salt-adapted cells [17].
• Sphingolipid activator protein-2 (SAP-2) has been found to stimulate the enzymatic hydrolysis of at least three sphingolipids, glucosylceramide, galactosylceramide and sphingomyelin [5].

Analytical, diagnostic and therapeutic context of ELK3

• Colonization of the RHVE by C. albicans SC5314 did not cause any visible epithelial damage 6 h after inoculation, although expression of SAP2, SAP9, and SAP10 was detected by reverse transcriptase PCR [1].
• ERP differences with vs. without concurrent fMRI [22].
• Isoelectric focusing followed by electroblotting and immunochemical staining demonstrated no significant difference in the charge of SAP-2 obtained from different cell lines [5].
• Using monospecific antibodies against SAP-2 the level of SAP-2 was determined in cultured skin fibroblasts by rocket immunoelectrophoresis [5].

References