Disease relevance of CSHL1

• Finally, in contrast to the detection of variable levels of hCS-L RNA in term placenta and hydatidiform mole samples, no hCS-L transcripts were detected in the three choriocarcinoma cell lines examined [1].
• Antibodies to cerebellar soluble lectin CSL in multiple sclerosis [2].
• We show that HsDPH3 is the previously described human diphtheria toxin and Pseudomonas exotoxin A sensitivity required gene 1 and that DPH4 encodes a CSL zinc finger-containing DnaJ-like protein [3].
• In this report, we have investigated the role of the CS5 sequence in melanoma cell adhesion and the identity of its receptor [4].
• These findings indicate that CSL has a functional role in sporozoite infectivity and is a candidate molecular target for passive or active immunization against cryptosporidiosis [5].

Psychiatry related information on CSHL1

• For these studies, a panel of epithelial and mesenchymal cell lines was examined for permissiveness to C. parvum and the ability to bind CSL [6].

High impact information on CSHL1

• Transcriptional activation requires the displacement of corepressors from CSL by the intracellular portion of the receptor Notch (NotchIC) and the recruitment of the coactivator protein Mastermind to the complex [7].
• Cerebrospinal fluid samples from 239 patients with various neurological disorders were tested for the presence of autoantibodies to an endogenous mannose-binding protein, the cerebellar soluble lectin CSL, by means of an immunoblotting test with rat CSL as antigen [2].
• The results of these analyses provide further, tentative, evidence for the presence of a CSL locus on the long arm of chromosome 4 and help to refine the location of this locus in the region of D4S175 and D4S192 [8].
• In addition, recent evidence of linkage between CL +/- P and two markers (D4S175 and D4S192) in the region 4q25-4q31.3 raised the possibility that a CSL, with a larger effect than either TGFA or RARA, may reside within this region of the human genome [8].
• In the ninth patient homozygous for a 7.6-kb deletion, the breakpoints are contained within a 29-bp perfect repeat lying 5' to GH1 and the human chorionic somatomammotropin pseudogene (CSHP1) [9].

Chemical compound and disease context of CSHL1

• When N-terminal cysteine derivatives of the CS peptides were conjugated to IgG by covalent cross-linking with N-succinimidyl-3(2-pyridyldithio)propionate, both the CS1 and CS5 conjugates promoted B16-F10 melanoma cell spreading [10].
• We hypothesized that neutralizing monoclonal antibodies (MAbs) targeting the apical complex and surface antigens CSL, GP25-200, and P23 could passively immunize against cryptosporidiosis [11].
• PATIENTS AND METHODS: Twenty patients with ulcerative colitis, intolerant or allergic to 5-ASA, have been treated with a new probiotic preparation (VSL#3, CSL, Milan, Italy) containing 5x10(11) cells/g of 3 strains of bifidobacteria, 4 strains of lactobacilli and 1 strain of Streptococcus salivarius ssp. thermophilus [12].
• A mechanism for the loss of contact inhibition is discussed based on the over-expression of CSL ligands in C6 glioblastoma cells relative to normal cells [13].
• There has been a marked increase in community concerns of the risk of food induced anaphylaxis in children and a consequent increase in the provision of the self or carer injectable epinephrine (EpiPen) (CSL Ltd, Parkville, Victoria, Australia)) [14].

Biological context of CSHL1

• Complex alternative splicing partially inactivates the human chorionic somatomammotropin-like (hCS-L) gene [15].
• In contrast, the hCS-L gene has been considered a pseudogene inactivated by loss of the normal intron 2 splice donor site [15].
• Previously our laboratory has shown that hCS-L transcripts are present in human placenta and that their levels are induced during the second trimester [15].
• Three of the defined hCS-L mRNAs contain an extended open reading frame similar to that present in the functional GH and CS genes [15].
• To complete the characterization of the hCS genes, the nucleotide sequence of the hCS-5 gene was determined [16].

Anatomical context of CSHL1

• To circumvent this problem, we have established stably transfected cell lines selectively expressing the hCS-L gene [15].
• The level of hCS RNA varied from 22-99% of the total hGH/hCS RNA in the neoplastic trophoblast samples, and variable levels of hGH-V and hCS-L RNA were also observed [1].
• Also, many term placentas from diabetic pregnancies express lower relative levels of hCS-L mRNA and a much higher hGH-V/CS-L mRNA ratio compared to normal term placenta, resembling more an early placenta pattern of expression [17].
• CSL was characterized as a soluble glycoprotein exoantigen released by infectious sporozoites [5].
• These observations indicate that the 85-kDa protein functions as a Caco-2 cell receptor for CSL [6].

Associations of CSHL1 with chemical compounds

• The minimal active sequence within CS5, the tetrapeptide Arg-Glu-Asp-Val (REDV), is somewhat related to the Arg-Gly-Asp-Ser (RGDS) sequence that represents a major active site in the central cell-binding domain (CCBD) of fibronectin [4].
• Analysis of 14 deletion and alanine substitution mutants revealed a correlation between CBF1 binding, CSL-mediated transactivation, and AP-1 repression [18].
• A previously proposed universal relation for the perpendicular component of the rotational diffusion tensor, R perpendicular, for CSL in PC/cholesterol mixtures (i.e., R perpendicular = R0 perpendicular exp(-AS2chol/RT)) is confirmed [19].
• These studies were performed over a range of blends of POPC and POPS and temperatures, utilizing the spin-labeled lipids 16-phosphatidylcholine and 5-phosphatidylcholine as well as cholestane (CSL) [20].
• However, being more polar, the nitroxide spin probe CSL is preferentially located near the surface of the membrane, while the less polar fluorescent probe DPH reports preferentially near the central hydrophobic region of the lipid bilayers [21].

Other interactions of CSHL1

• In addition, we have found several placental-specific hypersensitive sites downstream of the hCS-L and hCS-A genes, which might reflect the presence of enhancer elements similar to that located downstream of the hCS-B gene (Walker et al. (1990) J. Biol. Chem. 265, 12940) [22].
• The probe did not hybridise to DNA from CS3, CFA/III CS6, CS5 CS6, CS6, CS7, or PCFO159 ETEC [23].

Analytical, diagnostic and therapeutic context of CSHL1

• Sequence analysis revealed a mutation of the 5' splice site at the exon II-intron B boundary, suggesting that the hCS-5 gene is a pseudogene [16].
• Further, CSL was determined to be the molecular species mechanistically involved in the CSP-like reaction by its identification in SDS-PAGE gels and Western blots of purified membranous precipitates [5].
• The RHR of CSL contains both the N- and C-terminal beta-sheet domains (RHR-n and RHR-c) of typical Rel transcription factors, as judged by circular dichroism spectra [24].
• Immunoelectron microscopy demonstrated that CSL bound initially to the surface of Caco-2 cells and was rapidly internalized [6].
• The molecule bound by CSL was identified as an 85-kDa Caco-2 cell surface protein by radioimmunoprecipitation and CSL affinity chromatography [6].

References