Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ARCN1, KIAA0638, TREH, DDX6, BLR1, BCL9L, UPK2, DLNB13, DLNB14, RPS25, SBDN, G6PT1, HYOU1, VPS11, HMBS, H2AFX, DPAGT1, KIAA0285, MIZF, ABCG4, NOD9, PDZK2, CBL, MCAM, RNF26, C1QTNF5, MFRP, USP2, THY1, and PVRL1 genes are located within the commonly deleted region of neuroblastoma at human chromosome 11q23.3. Here, we characterized the KIAA0638 gene within the 11q23.3 region by using bioinformatics. Because human KIAA0638 gene was homologous to human LL5B gene encoding LL5beta protein, KIAA0638 was designated LL5A gene encoding LL5alpha protein. LL5A isoform 1 (FLJ00141 type) consists of exons 1-12, 14-21 and 23, while LL5A isoform 2 (KIAA0638 type) consists of exon 1-23. LL5A isoform 1 was the major transcript among LL5A isoforms generated due to alternative splicing. Nucleotide sequence of mouse Ll5a cDNA was determined by assembling CB522359 EST and 5'-truncated mKIAA0638 cDNA. Human LL5alpha isoform 2 showed 94.4 and 35.9% total-amino-acid identity with mouse Ll5alpha and human LL5beta, respectively. LL5alpha proteins consist of Forkhead associated (FHA) domain, bipartite nuclear localization signal (NLS), Chromosome segregation ATPases (SMC) domain, and Pleckstrin homology (PH) domain. LL5alpha proteins were homologous to PtdIns(3,4,5)P3 sensor protein LL5beta in the SMC and PH domains, and were also homologous to KIF1A, KIF1B, KIF13A, KIF13B, KIF14, and SNX23 proteins in the FHA domain. LL5alpha protein might be a transducer of PtdIns(3,4,5)P3 levels to the intracellular trafficking system.
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PMID:Identification and characterization of human LL5A gene and mouse Ll5a gene in silico. 1453 93

Macroautophagy/autophagy, a defense mechanism against aberrant stresses, in neurons counteracts aggregate-prone misfolded protein toxicity. Autophagy induction might be beneficial in neurodegenerative diseases (NDs). The natural compound trehalose promotes autophagy via TFEB (transcription factor EB), ameliorating disease phenotype in multiple ND models, but its mechanism is still obscure. We demonstrated that trehalose regulates autophagy by inducing rapid and transient lysosomal enlargement and membrane permeabilization (LMP). This effect correlated with the calcium-dependent phosphatase PPP3/calcineurin activation, TFEB dephosphorylation and nuclear translocation. Trehalose upregulated genes for the TFEB target and regulator Ppargc1a, lysosomal hydrolases and membrane proteins (Ctsb, Gla, Lamp2a, Mcoln1, Tpp1) and several autophagy-related components (Becn1, Atg10, Atg12, Sqstm1/p62, Map1lc3b, Hspb8 and Bag3) mostly in a PPP3- and TFEB-dependent manner. TFEB silencing counteracted the trehalose pro-degradative activity on misfolded protein causative of motoneuron diseases. Similar effects were exerted by trehalase-resistant trehalose analogs, melibiose and lactulose. Thus, limited lysosomal damage might induce autophagy, perhaps as a compensatory mechanism, a process that is beneficial to counteract neurodegeneration. Abbreviations: ALS: amyotrophic lateral sclerosis; AR: androgen receptor; ATG: autophagy related; AV: autophagic vacuole; BAG3: BCL2-associated athanogene 3; BECN1: beclin 1, autophagy related; CASA: chaperone-assisted selective autophagy; CTSB: cathepsin b; DAPI: 4',6-diamidino-2-phenylindole; DMEM: Dulbecco's modified Eagle's medium; EGFP: enhanced green fluorescent protein; fALS, familial amyotrophic lateral sclerosis; FRA: filter retardation assay; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GLA: galactosidase, alpha; HD: Huntington disease; hIPSCs: human induced pluripotent stem cells; HSPA8: heat shock protein A8; HSPB8: heat shock protein B8; IF: immunofluorescence analysis; LAMP1: lysosomal-associated membrane protein 1; LAMP2A: lysosomal-associated membrane protein 2A; LGALS3: lectin, galactose binding, soluble 3; LLOMe: L-leucyl-L-leucine methyl ester; LMP: lysosomal membrane permeabilization; Lys: lysosomes; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MCOLN1: mucolipin 1; mRNA: messenger RNA; MTOR: mechanistic target of rapamycin kinase; NDs: neurodegenerative diseases; NSC34: neuroblastoma x spinal cord 34; PBS: phosphate-buffered saline; PD: Parkinson disease; polyQ: polyglutamine; PPARGC1A: peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PPP3CB: protein phosphatase 3, catalytic subunit, beta isoform; RT-qPCR: real-time quantitative polymerase chain reaction; SBMA: spinal and bulbar muscular atrophy; SCAs: spinocerebellar ataxias; siRNA: small interfering RNA; SLC2A8: solute carrier family 2, (facilitated glucose transporter), member 8; smNPCs: small molecules neural progenitors cells; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; STED: stimulated emission depletion; STUB1: STIP1 homology and U-box containing protein 1; TARDBP/TDP-43: TAR DNA binding protein; TFEB: transcription factor EB; TPP1: tripeptidyl peptidase I; TREH: trehalase (brush-border membrane glycoprotein); WB: western blotting; ZKSCAN3: zinc finger with KRAB and SCAN domains 3.
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PMID:Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration. 3033 91