Disease relevance of ELK4

• 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].
• Lactosylceramide-loading studies confirmed that there was a defect in the turnover of this lipid in fibroblasts from the affected patient and fetus but not from a patient with an isolated SAP-1 deficiency, or from patients with Krabbe disease, GM1 gangliosidosis or galactosialidosis [2].
• SAP1 and SAP3 transcripts were observed only in patients with oral candidiasis [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].
• Transgenic mice were produced by microinjection of a human serum amyloid P component (hSAP) gene or a fusion gene (SS) comprising the promoter for hSAP (nucleotides -600 to -14 from the start codon) and the coding region of the hepatitis B virus surface antigen (HBsAg) [5].

Psychiatry related information on ELK4

• This region can be functionally replaced by fusion of Id proteins to SAP-1, whereby the Id moiety then acts to repress DNA binding in cis [6].

High impact information on ELK4

• Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element [7].
• SAP-1 has similar DNA binding properties to the previously characterized HeLa cell protein p62/TCF [8].
• 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 [9].
• 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) [9].
• The B-box dominates SAP-1-SRF interactions in the structure of the ternary complex [10].

Biological context of ELK4

• Secreted aspartyl proteinases (Saps), encoded by a gene family with at least nine members (SAP1 to SAP9), are one of the most discussed virulence factors produced by the human pathogen Candida albicans [11].
• Here, we have studied the role of HLH motifs in regulating DNA binding and transcription by the TCF protein SAP-1 and how Cdk-mediated phosphorylation affects the inhibitory activity of the Id proteins towards the TCFs [6].
• These docking domains are found in a range of substrates, including the transcription factors myocyte enhancer factor-2A and SAP-1 [12].
• The c-fos promoter contains a serum response element (SRE) that mediates ternary complex formation with the Ets proteins SAP-1 or Elk-1 and the MADS-box protein, serum response factor (SRF) [13].
• Comparison with the published nucleotide sequence for the precursor form of the human activator protein for sulfatide sulfatase (SAP-1) suggested that this activator also has a possibly glycosylated Asn and 6 Cys residues at similar positions, although the remainder of the molecule is somewhat different [14].

Anatomical context of ELK4

• Microarray analysis of stratifin-treated fibroblasts shows an increase in Elk4/Sap1 mRNA expression and this finding was confirmed by northern blot analysis [15].
• In contrast, SAP-1 and ELK-1 expression varied from one cell line to another [16].
• The reverse transcription-PCR protocol was used to determine which of the SAP1 to SAP7 genes are expressed by C. albicans during colonization and infection of the oral cavity [3].
• The endothelial cell interactions of homozygous null mutants of Candida albicans that were deficient in secreted aspartyl proteinase 1 (Sap1), Sap2, or Sap3 were investigated [17].
• The adhesiveness of delta sap1, delta sap2, delta sap3 null mutants and a triple delta sap 4-6 disruptant was examined on three surfaces--glass coated with poly-L-lysine or a commercial cell-free basement membrane preparation (Matrigel) and on human buccal epithelial cells [18].

Associations of ELK4 with chemical compounds

• When expressed separately, full length SAP1, SAP2, or the NH2-terminal domain alone, are able to assemble into filaments [19].
• This protein, ELK-1, and SAP-1 shared some unique structural properties such as an Ets DNA-binding site in the amino-terminal region, a serum response factor interacting domain and phosphorylation sites of serine or threonine residues in the carboxy-terminal region [20].
• SAP-1 is a sphingolipid activator protein found in human tissues required for the enzymatic hydrolysis of GM1 ganglioside and sulfatide [21].
• SAP-1 or sulfatide/GM1 ganglioside activator protein has previously been demonstrated to stimulate the enzymatic hydrolysis of sulfatide, GM1 ganglioside and globotriaosylceramide [22].

Physical interactions of ELK4

• Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex [13].

Other interactions of ELK4

• Three additional smaller regions show homology to the ELK-1 and SAP-1 genes, a subgroup of the ets gene family that interacts with the serum response factor [23].
• ELK4 (previously known as SAP-1 [SRF-associated protein-1]) is ubiquitously expressed [24].
• These data provide further evidence for a crucial role of Sap1 and Sap2 in C. albicans vaginal infections [1].
• Our results indicate that stratifin markedly increase Elk4/Sap1 mRNA expression in a time-dependent fashion [15].
• The characters high proteinase and increased virulence were not associated with a single molecular type or category identifiable through DNA fingerprinting or pulsed-field electrophoretic karyotype, and both SAP1 and SAP2 genes were present in both categories of isolates, on the same respective chromosomes [25].

Analytical, diagnostic and therapeutic context of ELK4

• The genes of two different aspartic proteinases from C. albicans, SAP1 and SAP2, with an overall homology of 77% in their nucleotide sequences, were chosen as targets for PCR [26].
• Using rabbit antibodies against human SAP-1 it could be visualized in extracts from cultured human skin fibroblasts after sodium dodecylsulfate-polyacrylamide gel electrophoresis, followed by electroblotting to nitrocellulose membrane and immunochemical staining (Western blotting) [21].
• In the rat extracorporeal circulation system, the hSAP level in the inlet blood to the IAM module decreased to 49% of the initial concentration within 60 min [27].
• To determine the value of the hSAP in human or rat plasma, we also developed a simple ELISA [27].

References