Disease relevance of NELL1

• NELL1 and NELL2 were predominantly expressed in neuroblastoma cell lines and little expressed in glioblastoma cell lines [1].
• NELL1 and NELL2 were also expressed in central neurocytoma, medulloblastoma, and some astrocytic tumors [1].
• Brain specific human genes, NELL1 and NELL2, are predominantly expressed in neuroblastoma and other embryonal neuroepithelial tumors [1].
• Additionally, the NELL1 and NELL2 mRNAs were found to be expressed abundantly in Burkitt's lymphoma Raji cells and colorectal adenocarcinoma SW480 cells, respectively [2].
• Human NELL-1 expressed in unilateral coronal synostosis [3].

Psychiatry related information on NELL1

• Potential interference by such self-stimulation is blocked by an inhibitory corollary discharge in the nucleus of the electrosensory lateral line lobe (NELL), the first central relay of the knollenorgan pathway [4].

High impact information on NELL1

• Previously, we reported NELL-1 as a novel molecule overexpressed during premature cranial suture closure in patients with craniosynostosis (CS), one of the most common congenital craniofacial deformities [5].
• Secondary sensory neurons in the nucleus of the electrosensory lateral line lobe (NELL) act as relays of peripheral responses [6].
• Runx2 bound to NELL-1 promoter in vivo [7].
• To study the transcriptional regulation of NELL-1, we analyzed the 5' flanking region of the human NELL-1 gene [7].
• The human NELL-1 messages were localized primarily in the mesenchymal cells and osteoblasts at the osteogenic front, along the parasutural bone margins, and within the condensing mesenchymal cells of newly formed bone in sites of premature sutural fusion [3].

Biological context of NELL1

• The cDNAs, designated NELL1 (nel-like, type 1) and NELL2 (nel-like, type 2), contained open reading frames encoding 810 and 816 amino acids, respectively [8].
• NELL1 is expressed mainly in tumors in the neuronal cell lineage [1].
• Two closely related genes coding for NELL proteins (NELL1 and NELL2) have been cloned by the yeast two-hybrid screening of a rat brain cDNA library with the regulatory domain of protein kinase C betaI (PKCbetaI) as bait [2].
• The nucleotide sequence of the full-length cDNA of this gene, human NELL-1, has approximately 61% homology with the chicken Nel gene [3].
• Identification of NAD+-dependent isocitrate dehydrogenase 3 gamma-like (IDH3GL) gene and its genetic polymorphisms [9].

Anatomical context of NELL1

• Mature NELL1 mRNA is not detected in any normal hemopoietic cell type, although the gene is transcribed during a narrow window of pre-B cell development, and cell lines at the same developmental stage express the NELL1 mRNA [10].
• Furthermore, while NELL1 and NELL2 show distinct subcellular localization in cytoplasm, they both are partially secreted into the culture medium of COS-7 cells [2].
• Although the NELL1 mRNA is faintly expressed in adult neural cells, the NELL2 mRNA is expressed abundantly, particularly in the pyramidal cells of rat hippocampus, showing neuronal high plasticity [2].
• In conclusion, our data suggest that the NELL-1 gene is preferentially expressed in cranial intramembranous bone and neural tissue (both of neural crest cell origin) and is up-regulated during unilateral premature closure of the coronal suture [3].
• We have identified a novel human gene designated as IDH3GL (isocitrate dehydrogenase 3 gamma-like) that is expressed specifically in human testis [9].

Associations of NELL1 with chemical compounds

• The NELL proteins expressed in COS-7 cells are homotrimeric glycoproteins and possess heparin-binding activity [2].
• The large cells and the NELL axons were identified by intracellular injection of biocytin and are physiologically similar [11].
• However, the emerging data from our group as well as others suggest that the signaling through NRP-1 actually promotes angiogenesis and is mediated through its C-terminal domain and downstream molecules such as phosphoinositide 3-kinase [12].

Other interactions of NELL1

• Here we demonstrate regulated expression of NELL1 and NELL2 in human hematopoietic cells [10].
• Both chicken Nel and human NELL-1 are comprised of six epidermal growth factor-like repeats [3].

Analytical, diagnostic and therapeutic context of NELL1

• 1. Sequence analysis of the IDH3GL cDNA revealed the presence of a premature stop codon at nucleotide positions 337-339 that results in a truncated peptide with 112 amino acids [9].
• By immunoprecipitation and in vitro phosphorylation assays, we have also found that NELL proteins expressed in COS-7 cells are associated with and phosphorylated by protein kinase C betaI (PKCbetaI) [13].
• Further analysis using various deletion mutants of NELL proteins by the yeast two-hybrid assay has revealed their EGF-like domains to be involved in the isoform-specific interaction with PKC [13].
• We report that little NRP-1 protein was detected in primary ovarian carcinoma tissues or established cell lines although mRNA for soluble and transmembrane NRP-1 were detected by RT-PCR [14].
• We performed immunohistochemistry assays using an anti-NRP-1 monoclonal antibody [15].

References